BCH475 Biochemistry of Carcinogens
Md. Ashrafuzzaman, D.Sc.
Known as: Dr. Ashraf
Email: mashrafuzzaman@ksu.edu.sa
Emergency contact cell: 0564174931
Office: 2B10, Bldg # 5, KSU
Biochemistry of Carcinogens
Carcinogens are agents that can cause cancer
Cancer
-The disease caused by an uncontrolled division of abnormal cells in a
part of the body.
-A malignant growth of tumor resulting from such a division of cells.
Normal cell, cancer cell and tumour
Comparison between the characteristics of normal and
cancer cells
Normal cells
Normal body cells have a number of important characteristics. They can
• Reproduce themselves exactly
• Stop reproducing at the right time
• Stick together in the right place
• Self destruct if they are damaged
• Become specialized or 'mature‘
• Show specific and normal functioning
Cancer cells
 Cancer cells are different to normal cells in several ways.
 They don't die if they move to another part of the body
 Cancer cells don’t stop reproducing
 Cancer cells violate signals from other cells
 Cancer cells stay immature and don’t specialize
 Cancer cells do not stick together
State of Cancer in USA
According to the National Cancer Institute, USA in 2010, the most
common cancers (excluding non-melanoma skin cancers) are listed
below.
Cancer type, Estimated new cases, Estimated deaths
Bladder 70,530 14,680
Breast (female-male) 207,090-1,970 39 840-390
Colon and rectal (combined) 142, 570 51 370
Endometrial 43,470 7 950
Kidney (renal cell) 53,581 11,997
Leukemia 43,050 21,840
Lung (including bronchus) 222,520 157,300
Melanoma 68,130 8,700
Non-Hodgkin lymphoma 65,540 20,210
Pancreatic 43,140 36,800
Prostate 217,730 32,050 Thyroid 44,670 1,690
The three most common cancers in men, women and children in the
U.S. are as follows:
Men: Prostate, lung, and colorectal
Women: Breast, colorectal, and lung
State of Cancer in Saudi Arabia and the world
According to the Saudi Cancer Registry
The average yearly number of cancer incidences reported in the Kingdom of Saudi Arabia over a decade
between 1997 and 2007 was 10,000.
Importantly, the yearly number has been found to show a tendency of fast growth in recent years.
The reporting sources for Saudi Cancer registry include all health care practitioners who diagnose or treat
cancer, as well as hospitals, clinical laboratories, and other cancer diagnosis and treatment facilities
within Saudi Arabia.
Due to heavy presence of foreign workers and professionals in Saudi Arabia who often avoid reporting their
cancer or other cases of diseases to the Saudi Cancer Registry the real number of the cancer cases in
the Kingdom is predicted to be much higher than the reported statistics.
World stages
In the world stages especially in the developed world countries where the disease screening and the
related medical statistics are most up-to-date the scenarios are found to be with dangerous trends.
US: According to a recent USA study overall 8% of adults aged 18 years and over had ever been told by a
doctor or other health professional they had some form of cancer. It also suggests that as age
increased, the percentage of adults who had ever been told by a doctor or other health professional
that they had cancer increased.
Canada: According to Canadian Cancer Society’s report, an estimated 177,800 new cases of cancer
(excluding about 74,100 non-melanoma skin cancers) and 75,000 deaths would occur in Canada in
2011. 29.6% of all deaths happened due to cancer in Canada in 2007. At the beginning of 2007, there
were approximately 748,897 Canadians who had been diagnosed with cancer in the previous 10 years.
This represents about 2.3% of the Canadian population or 1 out of every 44 Canadians.
World: According to 2002 report, worldwide, it is estimated that there were 10.9 million new cancer cases,
6.7 million deaths, 24.6 million persons living with cancer . The rates had been increasing since then.
Tumor
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An abnormal mass of tissue. Tumors are a classic sign of inflammation, and
can be benign or malignant (cancerous). There are dozens of different types
of tumors. Their names usually reflect the kind of tissue they arise in, and
may also tell you something about their shape or how they grow. For
example, a medulloblastoma is a tumor that arises from embryonic cells (a
blastoma) in the inner part of the brain (the medulla). Diagnosis depends on
the type and location of the tumor. Tumor marker tests and imaging may be
used; some tumors can be seen (for example, tumors on the exterior of the
skin) or felt (palpated with the hands).
Treatment is also specific to the location and type of the tumor. Benign
tumors can sometimes simply be ignored, or they may be reduced in size
(debulked) or removed entirely via surgery. For cancerous tumors, options
include chemotherapy, radiation, and surgery. See also blastoma,
carcinoembryonic antigen test, desmoid tumor, ear tumor, epidermoid
carcinoma, epithelial carcinoma, esophageal cancer, syringoma, fibroid,
tumor marker.
Tumor versus Cancer
A collection of pus is by definition a tumor. A cancer is a particularly
threatening type of tumor.
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neoplasm- An abnormal new growth of tissue that grows more rapidly than
normal cells and will continue to grow if not treated. These growths will
compete with normal cells for nutrients. This is a non-specific term that can
refer to benign or malignant growths. A synonym for tumor.
tumor- The more commonly used term for a neoplasm. The word tumor
simply refers to a mass. This is a general term that can refer to benign or
malignant growths.
benign tumor- A non-malignant/non-cancerous tumor. A benign tumor is
usually localized, rarely spreads to other parts of the body and responds well
to treatment. However, if left untreated, benign tumors can lead to serious
disease.
malignant tumor- Cancer. A malignant tumor is resistant to treatment, may
spread to other parts of the body and often recurs after removal. cancer- A
malignant tumor (a malignant neoplasm).
Anaplasia
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Anaplasia is the abnormal lack of differentiation in cells. It is
characteristic of malignant tumors and usually refers to a
reversal in cell differentiation. However, it can also refer to the
failure of cells to differentiate in the first place.
Many tissues in the human body contain stem cells, which are
undifferentiated and can self-renew through cell division. Being
undifferentiated means that stem cells are multipotent or
multidifferential; they can become one of several cell types
depending upon the needs of the body. For example, stem cells
in the bone marrow are able to differentiate into all the different
types of blood cells.
Anaplasia occurs when differentiated body cells return to an
undifferentiated state, often forming a tumor. Cells undergoing
anaplasia also often show an increased ability to multiply. Stem
cells that fail to differentiate properly can also be the source of
cancerous tumors.
Most body cells contain a nucleus, which can be considered the
control center of the cell and contains most of the cell's genetic
material. Cytoplasm fills the area between the cell membrane,
the outer boundary of the cell, and the nucleus. Cells that
undergo anaplasia are characterized by large, darkly-colored
nuclei and
large cytoplasm-to-nucleus ratios, 1:1 instead of the normal 1:4
or 1:6.
Anaplasia may result in cells with multiple nuclei, and the cells
-plasia
Anaplasia – dedifferentiation
Hyperplasia – physiological
proliferation Increase in number of
cells
Neoplasia – abnormal proliferation
Dysplasia – maturation abnormality
Metaplasia – cell type conversion
Prosoplasia – cell type develops
new function
Desmoplasia – connective tissue
growth
Anaplasia and plemorphism
Anaplastic cells display marked plemorphism where cells appear with marked
nuclear shape and size variation.
Tumorigenesis
Carcinogenesis or oncogenesis or tumorigenesis is literally the creation of cancer. It is a
process by which normal cells are transformed into cancer cells
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What causes cancer?
It is complex. Effects of many things like
exposure of carcinogens (various types)
tobacco use,
certain infectious,
radiation (persons working with radiation hazards),
lack of physical activity,
poor diet and obesity,
abnormal physical activity,
etc.
All these factors can directly or indirectly damage genes or combine with
existing genetic faults within cells to cause the disease.
Hereditary: 5-10% of cancers.
Tumorigenesis
By reducing ambient oxygen
exposure in de novo cancer
models, this study shows the
potential importance of oxygen
in influencing the initiation of
tumorigenesis.
Although large human
epidemiologic datasets have
correlated exposure to higher
altitudes with lower cancer
incidence, this study
demonstrates that lower
ambient oxygen levels delay
tumorigenesis, independent of
other variables such as
barometric pressure and
ultraviolet exposure associated
with high altitude
Ambient oxygen increases DNA damage and promotes tumorigenesis in cancer cell
p53−/− mice
Cell differentiation
Some tumors may experience
poor cell differentiation
Some cancer cells begin to
multiply before they are fully
mature. This causes disturbances,
both in the shape and structure of
the cell, and also possibly of the
architecture of the tumor as a
whole. The sooner the cells begin
to divide, the "wilder" they
become, both in the way they look,
and in their behavior. Tumors that
have a greater proportion of these
rapidly-dividing cells will grow
faster, and tend to spread earlier.
Such cancer is said to be more
aggressive.
Stem cell specific and
conventional cancer therapies
Apoptosis
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Apoptosis, or programmed cell death, is a normal component of the development
and health of multicellular organisms.
Controlled versus uncontrolled cell death. Cells die in response to a variety of
stimuli and during apoptosis they do so in a controlled, regulated fashion. This
makes apoptosis distinct from another form of cell death called necrosis in which
uncontrolled cell death leads to lysis of cells, inflammatory responses and,
potentially, to serious health problems.
Cell Suicide. Apoptosis, by contrast, is a process in which cells play an active role
in their own death (which is why apoptosis is often referred to as cell suicide).
Cell signalling and apoptosis. Upon receiving specific signals instructing the cells
to undergo apoptosis a number of distinctive changes occur in the cell. A family of
proteins known as caspases are typically activated in the early stages of apoptosis.
These proteins breakdown or cleave key cellular components that are required for
normal cellular function including structural proteins in the cytoskeleton and nuclear
proteins such as DNA repair enzymes. The caspases can also activate other
degradative enzymes such as DNAses, which begin to cleave the DNA in the
nucleus.
Apoptotic pathway
The receptor aggregation stimulates recruitment of FADD and caspase (casp) 8 activation, which
is regulated by cFLIP and growth factor signalling through the MAPK pathway. Casp 8 activation
leads to casp 3 cleavage, which initiates multiple proapoptotic processes, including CAD
stimulation of DNA cleavage. Through the mitochondrial pathway, prosurvival signaling through
AKT activation stimulates phosphorylation of BAD, which allows BCL2 to exert its antiapoptotic
effects by blocking proapoptotic proteins NOXA and BAX.
Biomarker in Apoptosis
PS externalization. Early in the apoptotic process there is a rapid redistribution and exposure of
phosphatidylserine (PS) on the cell surface mediated by the enzyme scramblase. PS is normally
restricted to the inner leaflet of the lipid bilayer by an ATPdependent enzyme called flippase
(translocase). Flippase, in concert with a second ATP-dependent enzyme, floppase, that pumps
cationic phospholipids such as phosphatidylcholine (PC) and sphingomyelin to the cell surface,
maintains an asymmetric distribution of different phospholipids between the inner and outer
leaflets of the plasma membrane.
Occupational Cancer
Occupational cancer is cancer that is caused wholly or partly by exposure to a carcinogen at work.
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How common is occupational cancer? The US data here gives an idea.
Type of Cancer
Lung
Bladder
Mesothelioma
Leukemia
Laryngeal
Skin Cancer (non-melanoma)
Sinonasal and nasopharyngeal
Kidney
Liver
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Related to Occupational Exposure %
6.3-13%
3-19%
85-90% (men); 23-90% (women*)
0.8-2.8%
1-20% (men)
1.5-6% (men)
31-43% (men)
0-2.3%
0.4-1.1 (vinyl chloride only; men)
In general, the overall attributable risk for mesothelioma in women is 23%. However, if the woman has had
"take-home" exposure to asbestos, the risk may be around 90%. "Take-home" exposure results from
asbestos being carried home on contaminated work clothing or other items.
Mesothelioma is a rare form of cancer that develops from transformed cells originating in the
mesothelium, the protective lining that covers many of the internal organs of the body. It is
usually caused by exposure to asbestos-silicate minerals.
Reference: Data From: Steenland, K., et al. Dying for work: the magnitude of US mortality from selected
causes of death associated with occupation. American Journal of Occupational Medicine. Vol. 43 (2003). p.
461-482
Extrinsic factors in Cancer
Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of polyamines and
pituitary factors.
Although polyamines are important in regulating proliferation of mammalian cells, their role in
hormone induction of cell growth has not been delineated.
It has have identified both intrinsic (polyamines) and extrinsic (pituitary/serum) factors that are
importance for estrogen to exert its mitogenic action.
Cell intrinsic & extrinsic factors in cervical
carcinogenesis
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Human papillomavirus (HPV) infection is a common sexually transmitted infection which a
majority of infected women are able to clear by mounting an effective immune response.
Individuals with a suboptimal immune response may be at increased risk of persistent HPV
infection leading to sequelae of various grades of dysplasias and / or associated malignancy.
HPV in cervical cancer progression. Human cervix is covered by squamous or columnar epithelium. The squamocolumnar junction
has certain reserve cells that can differentiate into either of the cell fate. HPV infects the basal cells of squamous epithelium. Viral
particles are released by the mature differentiated cells which can reinfect. With the expression of viral oncoproteins the lesions
progress from Low grade squamous intraepithelial Lesion (LSIL) to high grade (HSIL). The presence of estrogen and high expression
of viral proteins after the integration of the viral genome initiates squamous cell carcinoma (SCC) progression in the reserve cells of
transition zone.
Chimney-sweeps and cancer
A chimney sweep is a worker who clears ash and
soot from chimneys.
Chimney sweep's cancer called Soot wart
(formerly known as Percival Pott), is a
squamous cell carcinoma of the skin of the
scrotum.
It has the distinction of being the first reported form
of occupational cancer, 1775.
Pott was the first person to demonstrate that a
malignancy could be caused by an
environmental carcinogen.
How to avoid (first aid): Wash your body with clean
water immediately after work.
Dye workers and cancer of the lung
Luminous paint and bone cancer
Mining and lung cancer
UV-light and skin cancer
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5% of cancer in men
1% of cancer in women result from exposure
to carcinogenic substances in their work
environment:
lung and pleura
bladder
skin
laryngeal
nasal cavity
leukemia
Throat
lymphoma
soft-tissue sarcomas
Liver
Read more:http://www.answers.com/topic/occupational-exposures-andcancer#ixzz1mFMqdk3R
Such a Budhdha costume
is good to divert a lot of
work related cancers.
Think of its suitability,
confortability and
affordability.
Classification of carcinogens
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People are continuously exposed to varying amounts of chemicals that have been shown to
have carcinogenic or mutagenic properties in experimental systems.
Chemical carcinogens can occur exogenously or endogenously in living organisms (aerobic
metabolic processes, hormonal changes, oxygen uptake and distribution, pathophysiologic
states such as inflammation, genetic factors, etc.).
Exogenous exposure to carcinogens can occur through food consumption, air, occupational
exposure and drinking water.
Exposure to extrinsic or environmental carcinogens may 75-80% human cancers.
Epidemiology study suggests that lifestyle causes of cancer such as diet, tobacco smoking,
obesity, alcohol, random sex, etc., are the major contributors to human malignant neoplasms.
Old people are most vulnerable to carcinogens and other causes of cancers. Carcinogenesis
is a multistep process that affects to a great extent old age.
Youths are vulnerable to oral sex related cancer. The incidence of oral cancer due to a virus
transmitted during oral sex has increased steeply over the last 30 years. And scientists relate
this trend to changes in people's sexual behaviour. The number of tongue, mouth and throat
cancers due to the sexually transmitted human papilloma virus (HPV), which can also cause
cervical cancer in women, rose by about a third from 1973 to 2004.
The carcinogenic risk to chemical carcinogens is a composite of its effects on multiple genetic and
epigenetic processes.
Policy making. Various international and national agencies collect experimental data and risk
assessment studies on chemical carcinogens through in vivo studies on experimental animals
and in vitro studies in cell lines. They set the limits of exposure (especially in the working
environment) and legislate to restrict the use of chemical carcinogens in other applications.
A few specific types
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Genotoxicity. A deleterious action on a cell's genetic material affecting its integrity. Chemical
compounds and radiation both are responsible. Genotoxic substances have strong affinity to
interact with DNA, may cause potentially mutagenic or cancerogenic effects.
Activation-dependent and independent
effects.
(A) Microvessel density reduction by
intramuscular and intratumoral IL12
electrotransfer. (B) Morphological change in
microvessels in the tumors receiving
intramuscular IL12 electrotransfer. Treatment
was done by injection of the IL12 gene.
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Solid state hormones. Neuropeptides and
peptide hormones are packaged in a
concentrated condensed form maintaining
peptides in an aggregate or solid state.
Structure in biological systems. The acidic
environment helps this solid state/condensed
form.
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Carcinogenesis promoter. Promoters
represent cancer risk factors that are capable
of triggering the preferential multiplication of
initiated cells without having the potential to
initiate alone the process of carcinogenesis.
Promoters should be inactive at increasing the
risk of cancer when given alone.
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Immunosuppressant/immunotoxins. An
immunosuppressant is any substance that
performs immunosuppression of the immune
system. They may be either exogenous, as
immunosuppressive drugs, or endogenous, as
,e. g., testosterone. When the immune system
function is suppressed, there is an increased
susceptibility to infectious diseases and
cancers.
Procarcinogens
Procarcinogens are chemical substances that becomes carcinogenic only after they are
altered by metabolic processes.
Example: Nitrites-when taken in by the diet. They are not carcinogenic themselves, but turn
into nitrosamines in the body, which are carcinogenic.
Example: The drug diethylstilboestrol (a synthetic oestrogen no longer in clinical use) is
metabolized to an epoxide intermediate, which can cause cervical cancer.
Process. It is during some enzymatic process of detoxification of foreign chemicals that a
procarcinogen may be converted into an ultimate carcinogen
Ultimate carcinogens: these are direct acting because they possess the correct chemical.
Procarcinogens/precarcinogens: these require some kind of structural conversion. The
whole conversion process is known as bioactivation.
Fate of carcinogens??
Oxygenases or Oxidases
An oxygenase is any enzyme that oxidizes a substrate by transferring the oxygen from
molecular oxygen O2 (as in air) to it.
Types: There are two types of oxygenases:
• Monooxygenases, or mixed function oxidase, transfer one oxygen atom as a hydroxyl
group to the substrate, and reduce the other oxygen atom to water.
• Dioxygenases, or oxygen transferases, incorporate both atoms of molecular oxygen
(O2) into the product(s) of the reaction.[6]
Example: Among the most important monooxygenases are the cytochrome P450
oxidases, responsible for breaking down numerous chemicals in the body.
The monooxygenase reaction also requires a reduced substrate (NADH or NADPH) as
an electron donor, according to the following equation:
A + O2 + BH2 → AO + H2O + B
where A represents an organic compound and B represents the electron donor.
Oxygenase reactions in cells of higher plants
POLYCYCLIC AROMATIC HYDROCARBONS (PAHs) or
Polynuclear Aromatic Hydrocarbons, PNA
Numbers: ~ 10,000 compounds
Examples: Benzo(a)pyrene, Benzanthracene, Benzo(b)fluoranthene, Fluoranthene, Naphthalene,..
Sources. Mostly environment.
They are from incomplete burning of carbon-containing materials like oil, wood, garbage or coal.
Many useful products such as mothballs, blacktop, and creosote wood preservatives contain
PAHs. Special-purpose skin creams and anti-dandruff shampoos that contain coal tars. ETC.
• Automobile exhaust, industrial emissions and smoke from burning wood, charcoal and tobacco
contain high levels of PAHs. In general, more PAHs form when materials burn at low
temperatures, such as in wood fires or cigarettes. High-temperature furnaces produce fewer
PAHs.
• Fires can form fine PAH particles. They bind to ash particles and can move long distances
through the air. Some PAHs can dissolve in water. PAHs can enter groundwater from ash, tar,
or creosote that is improperly disposed in landfills.
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HOW ARE PEOPLE EXPOSED TO PAHs?
Breathing, drinking, eating, touching, etc.
Harmful health effects: Cancer, various organ systems, reproductive effects, etc.
PAHs cause breast cancer in humans! Liver cancer!
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Most carcinogens bind (covalent bond) with proteins, RNAs, DNAs. Lead to cancers.
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It is not known whether PAHs affect breast cancer risk in humans. Studies done to date are not conclusive.
Some of the research on PAHs and breast cancer in humans is summarized below.
Cigarette Smoking: While cigarette smoking is a major source of exposure to PAHs, most studies have not
seen a higher risk of breast cancer in women who smoke.
Workplace studies: A small number of studies have been conducted involving women with work exposure to
PAHs. None have shown an increased breast cancer risk.
Markers of exposure: More recent studies have begun to evaluate whether measurable markers (indicators)
of exposure to PAHs are associated with breast cancer risk. Once PAHs enter the body, they go to most
internal organs, especially those containing fat. Most PAHs are converted in the body to non-toxic materials
and leave the body in a few days in urine and bowel movements. Some become activated and bind to genetic
material (DNA) forming PAH-DNA adducts. PAH-DNA adducts are markers of PAH exposure. The formation
of DNA adducts is thought to be necessary for the development of cancer.
One study compared PAH-DNA adduct levels in 100 women with breast cancer to 105 women without breast
cancer. Twice as many of the women with breast cancer had high PAH-DNA adduct levels in their breast
tumors compared to the levels in breast tissue of women without breast cancer. However, the average levels
of DNA-PAH adducts was similar in the normal breast tissue of women with or without breast cancer. So,
while PAH-DNA adducts may be formed in greater numbers and accumulate in breast tumors, breast cancer
risk cannot be predicted from levels of PAH-DNA adducts in normal breast tissue.
Genetic differences: Studies are also underway to evaluate the risk of breast cancer due to differences in
genes (called genetic polymorphism). Certain genes affect the way the body activates or breaks down PAHs.
One gene of interest is called CYP1A1. In a study of 216 women with breast cancer and 282 women without
breast cancer, women with different types of the CYP1A1 gene (polymorphism of CYP1A1) who also smoked
cigarettes had a higher risk of breast cancer. A long-term national study, the Nurses Health Study, found no
overall increase in risk of breast cancer in women with different types of CYP1A1. The results suggested that
women with one type of CYP1A1 who had begun cigarette smoking before the age of 18 years were at
increased risk of breast cancer. However, this finding involved only eleven women with breast cancer, which
is a very small proportion of the total 466 breast cancer cases in the study. While not conclusive, these
findings should be investigated in further studies.
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Mid Term I, 25 marks-Performance indices
Excellent
MCQ: 25 marks
Mean=22.9, S.D.=1.4, No.=19
Poor
Written type (bonus): 2 marks
Mean=0.75, S.D.=0.6
Median=0.63
Median= 23
Min=0
Min=20(20)
Max=2
Max=24(25)
Recommendation!!!
Need to study more to understand the general concepts!
Aromatic amines
USED IN:
Tobacco smoke, diesel exhaust, formed in production of polyurethane foams, dyes, pesticides
and pharmaceuticals
FOUND IN:
plastic and chemical industries, as byproducts of the manufacturing of compounds such as
polyurethane foams, dyes, pesticides, pharmaceuticals and semiconductors. Environmental
pollution such as diesel exhaust, combustion of wood chips and rubber, tobacco smoke and
grilled meats and fish are other sources.
TYPES:
3 types of aromatic amines: monocylic, polycyclic and heterocyclic.
Some monocyclic amines, including o-toluidine (C7H9N), have been identified in the breast milk of
healthy lactating women. o-toluidine is known to cause mammary tumors in rodents. This
indicate that the mother’s mammary tissue and the nursing child are exposed to environmental
(mainly work related) carcinogens during breast-feeding.
Risk: breast cancer
Heterocyclic aromatic amines (HAAs) are formed, along with PAHs, when meats or fish are grilled
or otherwise cooked at high temperatures.
Risk: Increased amount of DNA adducts (in association with HAAs) that are indicators of
problems in DNA repair in cells, one of the early hallmarks of tumor development.
HAAs can mimic estrogen, and also can have direct effects on cell division processes in ways
that might enhance the development of tumors.
AZO dyes.
-Contain an azo group, -N=N-, which links two hybridised
carbon atoms. Often, these carbons are part of aromatic
systems.
-Azo dyes give bright, high intensity colours.
-azo compound class accounts for 60-70% of all dyes.
Aniline.
-an organic base used to make dyes, drugs, explosives, plastics, and
photographic and rubber chemicals.
-Aniline was first obtained in 1826.
-Chemical formula: C6H5NH2.
-Pure aniline is highly poisonous, oily, colorless with a pleasant odor
Benzidine.
the trivial name for 4,4'-diamino biphenyl, is the solid organic compound with the formula
(C6H4NH2)2. This aromatic amine is a component of a test for cyanide and also in the
production of dyes.
-Benzidine has been linked to bladder and pancreatic cancers.
Naphthylamine.
It is an aromatic amine. 1-naphthylamine sulfonic acids are used for
the preparation of azo dyes.
Aromatic amines and their conversion to ultimate carcinogens
Aromatic amines are indirectly acting carcinogens requiring multiple metabolic transformation to
hydroxylamines and their ultimate active form.
E.g. DNA Damage by Aromatic Amines – Are Arylamine Adducts responsible for the
Induction of the Chemical Carcinogenesis?
The initial step is an oxidation catalyzed by cytochrome of the arylamine to the corresponding Nhydroxylamine, followed by esterification into an N-acetoxyarylamine by N-acetyl transferase
(NAT) or into a sulfate by a sulfotransferase (ST) to give the ultimate carcinogens.
See here: http://www.chemie.uni-hamburg.de/oc/meier/research/oligos.html
DNA addducts.
a DNA adduct is a piece of DNA covalently bonded to a (cancer-causing) chemical. This process
could be the start of a cancerous cell, or carcinogenesis.
Covalent adducts between chemical mutagens and DNA. Such couplings activate DNA repair
processes and, unless repaired prior to DNA replication, may lead to nucleotide substitutions,
deletions, and chromosome rearrangements. This is the beginning of causing cancer.
• Chemicals which form DNA adducts include:
• acetaldehyde, is a significant constituent of tobacco smoke
• cisplatin binds to DNA and causes crosslinking, leading to death of the cell
• DMBA (7,12-dimethylbenz(a)anthracene)
• malondialdehyde, a naturally occurring product of lipid peroxidation[3]
See here: http://www.reference.md/files/D018/mD018736.html
Nitronium Ion
The nitronium ion, , NO+2, is a generally reactive cation created by the removal of an electron from
the paramagnetic nitrogen dioxide molecule, or the protonation of nitric acid.
• It is reactive enough to exist in normal conditions, but it is used extensively as an electrophile in
the nitration of other substances. The ion is generated in situ for this purpose by mixing
concentrated sulfuric acid and concentrated nitric acid according to the equilibrium:
2 H2SO4 + HNO3 → 2 HSO−4 + NO+2 + H3O+
-The aryl nitrenium ions are believed to be the ultimate reactive metabolites, which attack DNA to
form DNA adducts
Urinary Pathway
1. Human urinary system:
2. Kidney,
3. Renal pelvis,
4. Ureter,
5. Urinary bladder,
6. Urethra. (Left side with frontal section)
7. Adrenal gland
Vessels:
8. Renal artery and vein,
9. Inferior vena cava,
10. Abdominal aorta,
11. Common iliac artery and vein
With transparency:
12. Liver, 13. Large intestine, 14. Pelvis
Urinary bladder cancer
Definition of bladder cancer
Cancer that forms in tissues of the bladder (the organ that stores urine). Most bladder
cancers are transitional cell carcinomas (cancer that begins in cells that normally make up
the inner lining of the bladder). Other types include squamous cell carcinoma (cancer that
begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and
release mucus and other fluids). The cells that form squamous cell carcinoma and
adenocarcinoma develop in the inner lining of the bladder as a result of chronic irritation
and inflammation.
Estimated new cases and deaths from bladder cancer in the United States in 2012:
New cases: 73,510
Deaths: 14,880
Drugs Approved for Bladder Cancer
Adriamycin PFS (Doxorubicin Hydrochloride)
Adriamycin RDF (Doxorubicin Hydrochloride)
Cisplatin
Doxorubicin Hydrochloride
Platinol (Cisplatin)
Platinol-AQ (Cisplatin)
Biliary pathway
The biliary system is comprised of the organs
and duct system that create, transport, store
and release bile into the duodenum for
digestion. Includes the liver, gallbladder and
bile ducts (named the cystic, hepatic,
common, and pancreatic duct).
Bile (yellow material) in a liver biopsy in the setting
of bile stasis, i.e. cholestasis. H&E stain
• Action of bile salts in digestion
• Bile or gall is a bitter-tasting, dark green to
yellowish brown fluid, produced by the liver of
most vertebrates, that aids the process of
digestion of lipids in the small intestine. In
many species, bile is stored in the gallbladder
and upon eating is discharged into the
duodenum. Bile is a composition of the
following materials: water (85%), bile salts
(10%), mucus and pigments (3%), fats (1%),
inorganic salts (0.7%) and cholesterol (0.3%).
Intestinal cancer
(Also called: Duodenal cancer, Ileal cancer, Jejunal cancer, Small intestine cancer)
Your small intestine is part of your digestive system. It is a long tube
that connects your stomach to your large intestine. Intestinal
cancer is rare, but eating a high-fat diet or having Crohn's
disease, celiac disease, or a history of colonic polyps can
increase your risk.
Potential intestinal cancer symptoms:
• Abdominal pain, cramps (i.e., after eating)
• Unexplained weight loss
• Weak or tired feeling
• Nausea or vomiting
• Bloody stool
• A lump in the abdomen
• Jaundice
• Loss of appetite
Diagnosis: Imaging tests that create pictures of the small intestine
and the area around it can help diagnose intestinal cancer and
show whether it has spread.
Treatment: Surgery is the most common treatment. Additional
options include chemotherapy, radiation or a combination.
Intestinal Flora
Intestinal Flora
Intestinal flora are harmless microorganisms such as bacteria, yeasts, and fungi that
inhabit and grow in the intestines. These microorganisms are essential to the normal
functioning of the digestive tract, and certain species of intestinal flora are beneficial to
the human body. These “good” bacteria often have a symbiotic relationship with the
human body as both derive benefit from one another. For example, “The normal
[intestinal] flora derive from their host a steady supply of nutrients, a stable
environment, and protection and transport. The host obtains from the normal [intestinal]
flora certain nutritional and digestive benefits, stimulation of the development and
activity of immune system, and protection against colonization and infection by
pathogenic microbes.
Beneficial bacteria such as intestinal flora are often referred to a probiotics. “Probiotics...is
an umbrella term given to any live microorganism that is beneficial to its host.
Eat probiotic bacteria containing yogort regularly
Alkylating agents and related carcinogenesis
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A drug may be classified by the chemical type of the active ingredient or by the way it is used to
treat a particular condition. Each drug can be classified into one or more drug classes.
Alkylating agents are a class of chemotherapy drugs that bind an alkyl group (CnH2n+1) to DNA
and prevent proper DNA replication and transcription of RNA.
They have chemical groups that can form permanent covalent bonds with nucleophilic
substances in the DNA.
Alkylating agents are used as part of chemotherapy in different types of cancers.
Synthetic compounds containing alkyl groups that combine readily with other molecules.
The major site of action is on the base guanine.
They are primarily used in CHEMOTHERAPY of cancer (see ANTINEOPLASTIC THERAPY). However,
they do not damage malignant cells selectively, but also have a toxic action on normal cells; all
killing occurs primarily in rapidly proliferating tissue.
Different C4-alkanes and -cycloalkanes (left to right): n-butane
and isobutane are the two C4H10 isomers; cyclobutane and
methylcyclopropane are the two C4H8 isomers.
Bicyclo[1.1.0]butane is the only C4H6 compound and has no
isomer; tetrahedrane (not shown) is the only C4H4 compound
and has also no isomer.
Alkylating agents and related carcinogenesis
A drug may be classified by the chemical type of the active ingredient or by the way it is used to
treat a particular condition. Each drug can be classified into one or more drug classes.
• Alkylating agents are a class of chemotherapy drugs that bind an alkyl group (CnH2n+1) to DNA
and prevent proper DNA replication and transcription of RNA.
• They have chemical groups that can form permanent covalent bonds with nucleophilic
substances in the DNA.
• Alkylating agents are used as part of chemotherapy in different types of cancers.
• Synthetic compounds containing alkyl groups that combine readily with other molecules.
• The major site of action is on the base guanine.
• They are primarily used in CHEMOTHERAPY of cancer (see ANTINEOPLASTIC THERAPY). However,
they do not damage malignant cells selectively, but also have a toxic action on normal cells; all
killing occurs primarily in rapidly proliferating tissue.
Symptoms
-Locally they cause blistering of the skin and damage to the eyes and respiratory tract.
-Systemic toxic effects are nausea and vomiting, reduction in both leukocytes and erythrocytes,
hemorrhagic tendencies, amenorrhea or impaired spermatogenesis, damage to the intestinal
mucosa, and alopecia.
Among the agents of this group used in therapy are BUSULFAN, CYCLOPHOSPHAMIDE, IFOSFAMIDE,
and THIOTEPA; the NITROGEN MUSTARDSCHLORAMBUCIL, MELPHALAN, and MECHLORETHAMINE; and
the NITROSOUREASCARMUSTINE, LOMUSTINE, and STREPTOZOCIN.
Carcinogenesis in humans. Linked to bladder cancer and acute leukemia. However, the major
benefits obtained in treating diseases such as lymphoma, Hodgkin's disease, breast cancer,
and multiple myeloma far outweigh the risks of developing a second malignancy.
Mustard Gas
A poison gas attack using gas cylinders in
World War I.
The types of weapons employed ranged
from disabling chemicals, such as tear gas
and the severe mustard gas, to lethal
agents like phosgene and chlorine. This
chemical warfare was a major component
of the first global war and first total war of
the 20th century.
British soldiers blinded by mustard gas
British Gas
Casualties:
1914-18
Deaths
Non-Fatal
Chlorine
1,976
164,457
Mustard
Gas
4,086
16,526
Adolf Hitler
According to his own account in Mein Kampf, Adolf Hitler was temporarily blinded by gas
while healing in an hospital in Wervik. As a result, in part Hitler adamantly refused to
authorize the use of poison gas on the battlefield during World War II.
Mustard gas and cancer
The sulfur mustards, or sulphur mustards, commonly known as
mustard gas, are a class of related cytotoxic and vesicant chemical
warfare agents with the ability to form large blisters on the exposed skin
and in the lungs. Pure sulfur mustards are colorless, viscous liquids at
room temperature. When used in impure form, such as warfare agents,
they are usually yellow-brown in color and have an odor resembling
mustard plants, garlic or horseradish, hence the name.
The compound readily eliminates a chloride ion by intramolecular nucleophilic substitution to form a
cyclic sulfonium ion. This very reactive intermediate tends to permanently alkylate the guanine
nucleotide in DNA strands, which prevents cellular division and generally leads directly to
programmed cell death or, if cell death is not immediate, the damaged DNA may lead to the
development of cancer.
Synthesis
Sulfur mustard (Cl-CH2CH2)2S. In the Depretz method, it is synthesized by treating sulfur dichloride with ethylene:
SCl2 + 2 C2H4 → (Cl-CH2CH2)2S
In the Levinstein process, sulfur monochloride is used instead:
8 S2Cl2 + 16 C2H4 → 8 (Cl-CH2CH2)2S + S8
In the Meyer method, thiodiglycol is produced from chloroethanol and potassium sulfide and chlorinated with
phosphorus trichloride:
3 (HO-CH2CH2)2S + 2 PCl3 → 3 (Cl-CH2CH2)2S + 2 P(OH)3
In the Meyer-Clarke method, concentrated hydrochloric acid (HCl) instead of PCl3 is used as the chlorinating agent:
(HO-CH2CH2)2S + 2 HCl → (Cl-CH2CH2)2S + 2 H2O
Mustard gas , agents and treatment of Cancer
-Mustard gas, more properly called nitrogen mustard, is
an extremely toxic substance. Created by the
Germans in World War I,
-If respirators were not worn, the death rate was about 50
percent. Its exposure causes burning on the skin,
severe irritation of the lung tissues if the gas is
inhaled.
Discovery of mustard gas based Chemotherapy
During World War II, some soldiers who were
accidentally exposed to mustard gas were found to
have low white blood cell counts, leading doctors to
suspect the substance might have possibilities as a
chemotherapy agent.
White blood cells and cancer cells both grow rapidly, and
the theory was advanced that mustard gas might have
the same effect on cancer cells as it did white blood
cells. Some patients with advanced lymphomas -lymphoma is a cancer of the white blood cells -- were
given a form of mustard gas by vein. The patients
improved, although the effects were not long-lasting.
Nitrogen Mustard and Chemotherapy
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Nitrogen Mustard and Chemotherapy
Some drugs derived from nitrogen mustard are still used in chemotherapy today.
They are usually used in combination with other chemotherapy drugs.
Mustargen, mustine
Drug ‘mechlorethamine hydrochloride CH3N(CH2CH2Cl)2•HCl
are all forms of nitrogen mustard.
These medications are injected into the veins for lymphomas and cancers, and also
used as a lotion for skin lesions of one type of lymphoma. Nitrogen mustard
preparations are used in the treatment of Hodgkin's disease (white blood cells
originated cancer), non-Hodgkin's lymphoma, and as palliative chemotherapy in lung
and breast cancers. Palliative chemotherapy is not a cure, but is used to shrink
tumors or otherwise improve the quality of life.
Toxicity. Nitrogen mustard drugs are extremely toxic. In fact, they can actually cause
cancer as well as help cure it. Medical personnel who prepare these medications
must wear protective garb such as gloves and avoid inhaling the powder. According
to Drugs.com, treatment with Mustargen can result in the patient developing a
second malignant tumor, and the International Agency for Research on Cancer calls
it a "probable carcinogen," or cancer-causing agent.
Consideration. Although mustard gas in its original form is not used as a treatment for
lung cancer, nitrogen mustard derivatives are still in use.
Laboratory hazards-Chemicals
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What types of hazardous chemicals are present in laboratories?
Hazardous chemicals present physical or health threats to workers in clinical,
industrial, and academic laboratories. They include
carcinogens,
toxins,
irritants,
corrosives,
sensitizers,
hepatotoxins,
nephrotoxins,
neurotoxins
as well as
agents that act
on the hematopoietic systems (involved in blood production) or damage the
lungs, skin, eyes, or mucous membranes.
Current rules limit exposures to approximately 400 substances.
Chromosomal aberration
The exposure of cells to ionising radiations such as X-rays, γ-rays or charged particles can result
in an injury of different cellular constituents including DNA. DNA, which carries the genetic
information of the cell, is the most critical target. In higher organisms the DNA is organised in
chromosomes. During interphase (growth phase of the cell) the chromosomes are long, thin
threads that are individually indistinguishable. During cell division (mitosis) chromosomes
reach their highest degree of condensation.
A chromosome anomaly, abnormality or aberration reflects an atypical number of
chromosomes or a structural abnormality in one or more chromosomes. Cancer causing
agents are often responsible.
Chromosomes are composed of long thin molecules of DNA. When cells are exposed to radiation
or carcinogens, DNA sometimes breaks, and the broken ends may rejoin in different patterns
from their original arrangement. The abnormalities that result are termed "chromosome
aberrations" and may be visualized at mitosis when cells divide.
Metaphases labeled with fluorescence in situ
hybridization (FISH).
The left metaphase shows a normal cell and
the right, a translocation indicated by arrows
The frequency of chromosome aberrations increases
with radiation dose to the cells and serves as an
indicator of radiation dose received, i.e., a biological
dosimeter.
Chromosomal aberration-quantification
The frequency of chromosome aberrations increases with radiation dose to the cells and
serves as an indicator of radiation dose received, i.e., a biological dosimeter.
Cancer
Cancer
Cancer
World war II: USA bombed Japan
Relationship between fraction of cells with chromosome aberrations and radiation
dose to AHS survivors exposed in typical Japanese houses
Nitrosamines
Nitrosamines are chemical compounds of the chemical structure
R1N(-R2)-N=O
R stands for amine group (chemical compounds derived from ammonia)
90% of nitrosamines are carcinogenic.
Discovery
over 100 years ago, but not until 1956 did they receive much attention.
In 1956 John Barnes and Peter Magee reported that dimethylnitrosamine produced liver
tumors in rats.
In the early 1970s, there were outbreaks of liver disorders, including cancer, in various
farm animals in Norway. Intensive investigations revealed that all of the affected
animals had consumed rations containing herring meal (protein feed supplement),
which had been preserved by the addition of relatively large amounts of sodium
nitrite. Further investigation showed that the herring meal contained
dimethylnitrosamine, the same compound that Magee and Barnes had reported as a
strong liver carcinogen nearly a decade earlier. Dimethylnitrosamine was formed in
the fish meal as a result of a chemical reaction between dimethylamine, a commonly
occurring amine in fish meal, and
Nitrosamines in Food, Body Fluids, and
Occupational Exposure
Fried bacon
Cured (preserved) meats
Beer
Nonfat dry milk
Tobacco products
Gastric juices
Rubber products
Rubber manufacturing
Metal industries,
Pesticide production and use
Certain cosmetics
Certain chemical manufacturing
ETC.
Nitrosamines and cancer
Physical appearance in stomach: yellow liquid
Tobacco-specific nitrosamines
These nitrosamine carcinogens are formed from nicotine and related compounds by a
nitrosation reaction that occurs during the curing and processing of tobacco.
Example: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'nitrosonornicotine (NNN) are the most carcinogenic.
Cancer
NNK and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are potent
systemic lung carcinogens in rats. Tumors of the nasal cavity, liver, and pancreas are
also observed in NNK- or NNAL-treated rats.
NNN is an effective esophageal carcinogen in the rat, and induces respiratory tract
tumors in mice, hamsters, and mink.
A mixture of NNK and NNN caused oral tumors when swabbed in the rat oral cavity.
Cancer types
Lung, pancreas, esophagus, and oral cavity in people who use tobacco products.
Nitrates and Nitrites may also cause Alzheimer's, Diabetes and Parkinson's diseases
Carcinogenesis by Hormones
A hormone is a chemical released by a cell or a gland in one part of the body that sends out
messages that affect cells in other parts of the organism.
A small amount of hormone can alter cell metabolism. In essence, it is a chemical messenger
that transports a signal from one cell to another. All multicellular organisms produce
hormones.
Hormones in animals are often transported in the blood. Cells respond to a hormone when they
express a specific receptor for that hormone. The hormone binds to the receptor protein,
resulting in the activation of a signal transduction mechanism that ultimately leads to cell
type-specific responses.
Effects of hormones
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Amine-derived hormones
Peptide hormones
Lipid and phospholipidderived hormones
Etc.
stimulation or inhibition of growth
mood swings
regulation of apoptosis
activation or inhibition of the immune system
regulation of metabolism
preparation of the body for mating, fighting, fleeing, and other activity
preparation of the body for a new phase of life, such as puberty, parenting, and menopause
control of the reproductive cycle
hunger cravings
sexual arousal
A hormone may also regulate the production and release of other hormones.
Carcinogenesis by Hormones
Hormone-related cancers:
Breast,
Endometrium (the inner membrane of the mammalian uterus),
Ovary,
Prostate,
Testis (organ that produces sperm)
Thyroid
Osteosarcoma, a cancerous (malignant) bone tumor that usually develops during the
period of rapid growth that occurs in adolescence, as a teenager matures into an
adult.
Cervical cancer
Vaginal cancer, Etc.
These cancers share a unique mechanism of carcinogenesis.
Endogenous and exogenous hormones drive
cell proliferation (an increase in the number of cells as a result of cell growth and cell
division),
and thus the opportunity for the accumulation of random genetic errors.
The emergence of a malignant phenotype depends on a series of somatic mutations (a
genetic mutation that occurs in a somatic cell after conception/division. These can
lead to a variety of medical conditions)
Horomonal imbalance and its effects
• Causes of Hormone Imbalance
• Natural ways: in puberty, menopause and perimenopause, etc.
• Due to toxins or an unbalanced lifestyle.
Results: various hormone related cancers
Adrenal Hormone Balance and Breast Cancer Risk
Hormone balance is deeply connected to the food we eat, the exercise we get, the
toxins we absorb, the weight we carry, and the stress levels we put up with. How
these multiple factors impact the overall hormone picture is crucial, particularly at
midlife when most hormone production is taken over by the adrenal glands.
Cervical and Vaginal cancer
Cervical cancer is the term for a malignant neoplasm arising from cells originating in
the cervix uteri. One of the most common symptoms of cervical cancer is abnormal
vaginal bleeding, but in some cases there may be no obvious symptoms until the
cancer has progressed to an advanced stage.
Treatment: usually surgery in early stages, and chemotherapy and/or radiotherapy in
more advanced stages of the disease.
• Cancer screening using the Pap smear can identify precancerous and potentially
precancerous changes in cervical cells and tissue.
In developed countries, cervical screening programs have reduced cancer by 50%
Physical carcinogenesis
“physical carcinogens” includes a wide range of agents: electromagnetic radiations of different
kinds, corpuscular (alpha and beta) radiations, low and high temperatures, mechanical traumas,
and solid and gel materials. More restrictively, however, the term is ordinarily used to define
solid and gel materials, water insoluble or slightly soluble, that are capable of producing cancer.
The best known example is high-energy radiation, including nuclear radiation and X-rays.
Radiation. Because ionising radiation is of sufficiently high energy to disrupt electrons from atoms
it is the most dangerous type of radiation for all living organisms. 'The harmful effects of atomic
or ionizing radiation have been known since the early discoveries of Roentgen, Becquerel and
Madame Curie, but the present impacts and mechanisms of nuclear pollution are still not fully
understood. Radiation penetrates biological matter and acts on the cells and their constituent
parts by causing chemical, molecular or physical damage often resulting in cell death or genetic
mutation. Unlike most toxic chemicals, with radiation there appears to be no level of dose below
which damage cannot be caused.'
Examples of some sources of ionizing radiation that we live with: 'natural sources – the sun (UV
rays), uranium and radon, and building materials containing these elements
• industrial sources – fallout from man-made nuclear explosions and power station accidents
• medical sources – X-rays
• domestic sources – cathode ray tubes (computers and TVs), some smoke alarms and
fluorescent dials
• our bodies – radioactive elements e.g. potassium (natural) and strontium-90 (man-made
nuclear fission product [stored in our bones]).'
Physical carcinogenesis
Electromagnetic field non-ionising radiation Electromagnetic Fields (EMFs) are long-wave forms of
non-ionising radiation. EMF emissions in the environment come from natural sources e.g. the sun, the
earth's magnetic field and from manufactured sources e.g. highvoltage power lines, power
transmission stations and electrical appliances such as computers, electric blankets, hairdryers, TV
sets and microwave ovens. 'Risks posed by EMFs depend on the distance from source and duration
of exposure. For instance, transmission lines located only 200 to 300 feet away expose people to
fewer EMFs than many common domestic appliances … substantial evidence … strongly suggests
the carcinogenicity of EMFs … at least eighteen occupational studies link EMF exposure to leukemia,
five to brain cancer and thirteen to other cancers, including breast cancer.'
EMFs and melatonin EMFs interfere with the normal production of melatonin, a hormone of particular
significance when studying the causes of breast cancer. Melatonin is: 'a hormone made by the pineal
gland deep within the brain … [it] is only secreted at night and is an important regulator of the body's
24 hour clock. It also regulates various hormones, including oestrogen. Laboratory tests have shown
that melatonin also suppresses the growth of human breast cancer cells.'
(Read 1995) Working or sleeping in a situation of near-constant and bright, artificial 'light at night'
(LAN) may interfere with the normal production and work of melatonin. Many scientists consider
regular exposure to LAN an added risk for breast cancer since it can affect regulatory control of
oestrogen (the hormone most strongly associated with breast cancer) as a result of LAN impact on the
pineal gland. 'Sleep interruption, especially in women working the graveyard shift, is associated with
an increased risk of breast cancer.’
There can be no doubt that a major cause of cancer today is our involuntary exposure to carcinogens from
an ever increasing number of sources in our environment, from higher-than-normal levels of
background radiation in our homes to hazardous chemicals in products. Although our knowledge of
cancer is incomplete, we do have sufficient understanding of the processes involved to know that
cancer incidence can be reduced.
Inorganic carcinogenesis
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Arsenic related carcinogenesis. Mostly found saline water-south Asian
regions espceailly in Bangladesh and parts of India.
arsenic, cadmium, and lead as inorganic carcinogenesis
Inorganic Arsenite-Induced Malignant Transformation of Human Prostate
Epithelial Cells
Roentgens, Rads and Rems
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A Roentgen is a measure of the amount of charge produced in a particular sample of
air from ionizing radiation (i.e. - a type of radiation that has enough energy to remove
an electron from an atom, producing ions). The technical definition is the amount of X
or gamma radiation that produces one electrostatic unit of ionic charge in one cubic
centimeter of dry air at standard temperature and pressure. The Roentgen describes
the exposure of air from a radioactive source.
Radioactive decay produces various types of radiation in the form of particles (alpha,
beta, neutron) and photons (x-rays, gamma rays). A radioactive source will emit
these radiations at various frequencies, depending on its activity and its decay mode.
Each type of radiation, depending on its energy, produces a different amount of
ionization of air, and hence a different exposure. Alpha particles, for example, will
produce substantially different amounts of ionization than highly penetrating gamma
photons. The total exposure produced from a radioactive source is therefore related
to the total number and type of radiation emissions from that source; the total number
of emissions is related to the activity of that source.
Radiation units
Measures Relative to the Biological Effect of Radiation Exposure
• There are five measures of radiation that radiographers will commonly encounter when
addressing the biological effects of working with X-rays or Gamma rays. These measures are:
Exposure, Dose, Dose Equivalent, and Dose Rate A short summary of these measures and
their units will be followed by more in depth information below.
• Exposure: Exposure is a measure of the strength of a radiation field at some point in air. This
is the measure made by a survey meter. The most commonly used unit of exposure is the
roentgen (R).
• Dose or Absorbed Dose: Absorbed dose is the amount of energy that ionizing radiation
imparts to a given mass of matter. In other words, the dose is the amount of radiation absorbed
by and object. The SI unit for absorbed dose is the gray (Gy), but the “rad” (Radiation Absorbed
Dose) is commonly used. 1 rad is equivalent to 0.01 Gy. Different materials that receive the
same exposure may not absorb the same amount of radiation. In human tissue, one Roentgen
of gamma radiation exposure results in about one rad of absorbed dose.
• Dose Equivalent: The dose equivalent relates the absorbed dose to the biological effect of
that dose. The absorbed dose of specific types of radiation is multiplied by a "quality factor" to
arrive at the dose equivalent. The SI unit is the sievert (SV), but the rem is commonly used.
Rem is an acronym for "roentgen equivalent in man." One rem is equivalent to 0.01 SV. When
exposed to X- or Gamma radiation, the quality factor is 1.
• Dose Rate: The dose rate is a measure of how fast a radiation dose is being received. Dose
rate is usually presented in terms of R/hour, mR/hour, rem/hour, mrem/hour, etc.
One roentgen equals one rad and since the quality factor for x- and gamma rays is one,
radiographers can consider the Roentgen, rad, and rem to be equal in value.
Oncogenic viruses
A virus capable of inducing the formation of tumors. Also called tumor virus.
Cancer virus, tumor virus Oncology A DNA virus or RNA virus capable of causing
malignant transformation of cells, inducing a neoplasia in its host or causally linked to
human tumors. Oncogenic viruses include Retroviruses, eg leukemia viruses of cats,
cattle, chickens; Herpesviruses, eg EBV-induced Burkitt's lymphoma, Asiatic
nasopharyngeal carcinoma; DNA virus, eg HPV.
Rous sarcoma virus (RSV)
is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in
chickens.
In 1911, Peyton Rous discovered that cancer could be induced in healthy chickens by
injecting them with a cell-free extract of the tumor of a sick chicken.
Shope papilloma virus
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The cottontail rabbit papilloma virus (CRPV), or Shope papilloma virus, is a
type I virus under the Baltimore scheme, possessing a nonsegmented dsDNA
genome. It infects rabbits, causing keratinous carcinomas, typically on or near the
animal’s head. These tumors can become large enough that they interfere with
the host’s ability to eat, eventually causing starvation.
Shope papillomavirus provided the first mammalian model of a cancer caused by
a virus. It takes its name from Dr. Richard E. Shope, who discovered it in the
1930s. Shope was able to isolate virus particles from tumors on captured animals
and use these to inoculate domestic rabbits, which then developed similar tumors.
The virus was sequenced in 1984, showing substantial sequence similarities to
HPV1a. It has been used as a model for human papillomaviruses both before and
after this discovery. The most visible example of this role is the HPV vaccine,
which was developed based on and incorporating research done using the virus
as a model. Similarly, it has been used to investigate antiviral therapies.
Viruses and Cancer
The murine leukemia viruses (MLVs or MuLVs) are retroviruses named for their ability
to cause cancer in murine (mouse) hosts. Some MLVs may infect other vertebrates.
MLVs include both exogenous and endogenous viruses. Replicating MLVs have a
positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA
intermediate via the process of reverse transcription
Nodule-Inducing Virus. An exogenous, infectious mouse mammary tumor virus isolated
from BALB/cNIV/Crgl mice, thought to be derived from the endogenous low
oncogenic mouse mammary tumor virus found in C3Hf mice. (from Cancer Res.
1984 Oct;44(10):4333-6) Nodule-Inducing Virus is part of the Mouse Mammary
Tumor Virus group Nodule-Inducing Virus is also know as: Niv
osteogenic virus. Human osteogenic sarcoma cells transformed by murine sarcoma
virus (R97o) showed restricted growth of human cytomegalovirus (HCMV).
Carcinogenesis in Foods
Good food is good for health, bad food is bad for health, may cause diseases
Cancer versus Food
Oropharynx-Alcohol
Oesophagus-Alcohol and tobacco consumption Poor Nutrition
Stomach-Low intake of fresh vegetables High intake of starchy roots High intake of burnt,
barbequed, smoked, salted, fermented or pickled foods
Colon / Rectum-Meat and animal fat Low intake of cereals and vegetables (fibres) Smoking
Breast (post-menopausal)-High intake of animal fat
Endometrium (internal lining of the uterus)-High intake of fat and calorie
Prostate-High intake of fat and calorie
Liver-Alcohol and tobacco consumption Mycotoxins
Comparative diet-related cancer rates in Asia and other parts of the world.
Stomach cancer (also called gastric cancer) is much more common in Asia than in North
America, Western Europe and Australasia.
Oesophageal cancer is common across a broad area in Asia, stretching from east of the
Caspian Sea through China, Japan, and southern part of the Former Soviet union.
Liver cancer is common in Eastern Asia and in parts of Africa.
Animal results and extrapolation to man
(understanding carcinogenesis or effects)
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Bioinformatics
Model cell studies
Model Mouse studies
Small animal studies
Comparative animal studies
Human clinical studies
Goal:
Organ specificity, Genetic response, Dose level, etc.
Pyrrolizidines in herbal medicine
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Pyrrolizidine alkaloids (PAs) are a group of naturally occurring alkaloids based on the
structure of pyrrolizidine. Pyrrolizidine alkaloids are produced by plants as a defense
mechanism against insect herbivores. More than 660 PAs and PA N-oxides have been
identified in over 6,000 plants, and about half of them exhibit hepatotoxicity.[1] They are found
frequently in plants in the Boraginaceae, Asteraceae, Orchidaceae and Leguminosae families;
less frequently in the Convolvulaceae and Poaceae, and in at least one species in the
Lamiaceae. It has been estimated that 3% of the world’s flowering plants contain pyrrolizidine
alkaloids.[2] Honey can contain pyrrolizidine alkaloids,[3][4], as can grains, milk, offal and eggs.
Herbal does not necessarily mean it is always safe
Pyrrolizidine Alkaloids - Tumorigenic Components in Chinese Herbal Medicines and
Dietary Supplements-research finding (2002).
Laboratory hazards
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chemical and biological hazards
leaks, spills and unplanned releases
hazardous waste management
fires and explosions
safety legislation
precautions and safe practices
occupational health and hygiene monitoring
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protective equipment
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Eating, Smoking, noisy practices, teasing, etc.
Prevention-carcinogenesis perspectives
Prevention of carcinogenesis and inhibition of cancer, tumor by
• Better dietary practices
• Screening-regularly
• Consider better social practices
• Avoid contamination
• Take proper medication
• Etc.
List of small projects
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Tumor versus cancer-a general understanding
Occupational cancer-history, evidence and general overview
Cancer that is associated with social values and sexual causes
Carcinogens-classification and their effects on biological systems
General statistics on cancer in Saudi Arabia and in the world
Anaplasia and tumorigenesis
Groups
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Group 1. (Project 1)
428108339, 427106859, 426106691
Group 2. (Project 2)
428106483, 428101483, 427105632, 428107579
Group 3. (Project 3)
428108661, 428100033, 428108260
Group 4. (Project 4)
428108600, 428104677, 428105619
Group 5. (Project 5)
428107173, 428104332, 428108727
Group 6. (Project 6)
425106826, 428105842, 428114422
Project due: by first week, April, 2012
A few sample questions
Q. 1: Which one is cancerous cell? Circle two.
A. Normal functioning cell
B. Cell that shows abnormal cell division
C. Cell that shows abnormal shape and size.
D. Cell that divides normally
Q. 2: A malignant growth of tumor causes cancer. Circle one.
A. True
B. False
C. Not applicable for cancer
Q. 3: Cancer is cell related disease. Circle one.
A. True
B. False
Q. 4: Cancer can also be hereditary. Circle one.
A. True
B. False
Q. 5: Cells stick together at right place. Circle one.
A. applicable for cancerous cells
B. applicable for normal cells
Q. 5: Cells don't die if they move to another part of the body. Circle one.
A. applicable for cancerous cells
B. applicable for normal cells
Q. 5: Aging is not a factor for cancer. Circle one.
A. True
B. False
Q. 6: Smoking is primarily responsible for (circle one)
A. Hereditary cancer
B. Blood cancer
C. Lung cancer
Q. 7: Aged people have less risk of having cancer (circle one)
A. True
B. False
Q. 8: Profession of a person can never be a cause of cancer. Circle one.
A. True
B. False
C. Irrelevant
Q. 9: A person working in a cigarette factory has high risk to get the following cancer (circle one).
A. Prostate
B. Blood
C. Lung
D. Breast
Q. 10: A person eating fast foods regularly has high risk to get the following health problem (circle one).
A. Obesity
B. Eye problem
C. Breathing
D. None of the above
Q. 11: Tumor and cancer are same (circle one).
A. True
B. False
Q. 12: Cancer is not a major problem or disease in economically developed countries in Europe and North America
(circle one).
A. True
B. False
Q. 13: Cancer is mainly poverty related disease (circle one).
A. True
B. False
Q. 14: Cancer is not any considerable disease in Saudi Arabia (circle one).
A. True
B. False
Q. 15: There are appropriate medicines to treat all kinds of cancers (circle one).
A. True
B. False
Q. 16: Poor cell differentiation can be a cause of cancer (circle one).
A. True
B. False
C. Irrelevant
Q. 17: Anaplastic cells display marked plemorphism (circle one).
A. True
B. False
Q. 18: Cells that undergo anaplasia are characterized by cytoplasm to nucleus ratios (circle one).
A. 1:1
B. 1:4
C. 1:6
Q. 19: A tumor just under skin should be treated by (circle best one).
A. chemotherapy
B. operation
C. radiation therapy
D. other
Q. 20: A malignant tumor can cause cancer (circle best one).
A. yes
B. no
C. not applicable
Q. 21: A collection of pus is by definition (circle best one).
A. cancer
B. tumor
Q. 22: No cancer is recoverable (circle one).
A. Yes
B. No
Q. 23: Breast cancer is common among the following sex group (circle one).
A. Male
B. Female
B. Both Male and Female
Q. 24: Prostate cancer is common among the following sex group (circle one).
A. Male
B. Female
B. Both Male and Female
Q. 24: Anaplasia is characteristic of malignant tumor (circle one).
A. True
B. False
B. Not applicable
Q. 25: Anaplasia refers to reversal in cell differentiation (circle one).
A. True
B. False
B. Not applicable
26. Stem cells that fail to differentiate properly can also be the source of cancerous tumors. (circle one)
A. True
B. False
C. Irrelevant
27. Cells with alaplasia are often abnormally large. (circle one)
A. True
B. False
C. Irrelevant
28. Tumorigenesis does not rely on oxygen level. (circle one)
A. True
B. False
C. Irrelevant
29. People living in higher altitudes (on mountains) are found to have less probability to get cancer. (circle one)
A. True
B. False
C. Irrelevant
30. Ambient oxygen increases DNA damage and promotes tumorigenesis in cancer cell. (circle one)
A. True
B. False
C. Irrelevant
31. Cancer is an infectious disease. (circle one)
A. True
B. False
C. Irrelevant
32. If both husband and wife are found to get same type of cancer which one is probably true statement. (circle best one)
A. The cancer is hereditary
B. The cancer is infectious
C. Both of A and B
D. None of A and B