Mutagens and their actions
Chan Ho Yin, Aurora (02690763)
Chen Yiwei, Echo (01790443)
Co Ngai Na, Chloe (02715283)
Lam Kit Ming, Germaine (02770293)
Introduction
„
Mutation
„
„
Mutagen
„
„
„
„
Spontaneous Mutation & Induced Mutation
Chemical Mutagens
Radiation
Biological Mutagens
Conclusion
Mutation
„
The process that produces an inheritable
alteration in
„
„
„
DNA Structure
Chromosome Structure
There are two types of mutations
„
„
Spontaneous Mutation
Induced Mutation
Spontaneous Mutation vs.
Induced Mutation
„
Spontaneous Mutation
„ Natural error during DNA replication or
recombination
„ Caused by background radiation
„ Arise randomly as a result in cells
„ NO ARTIFICIAL TREATMENT
Spontaneous Mutation vs.
Induced Mutation
„
Induced Mutation
„ Caused by exposure to known
mutagenic agents
-- Mutagens
Mutagen
„
A natural or human-made agent
which can alter the structure or
sequence of genetic material and
induce
Mutation
„
There are three main types of
mutagens classifying by their
sources
„ Chemical Mutagens
„ Radiation
„ Biological Mutagens
Chemical
Mutagens
Radiation
Biological
Mutagens
• Base analogs • Ionizing
• Transposable
• Chemical
Radiation
element
modification • UV Radiation
agents
• Intercalating
agents
Chemical Mutagens -Base analogs
„
„
„
Chemicals structurally resemble normal
bases, purines and pyrimidines
Incorporate into DNA during replication
Lead to incorrect insertion of nucleotides
opposite them in replication
For Example
„
5-Bromouracil (5-BU)
„
2-Aminopurine (2-AP)
5-Bromouracil
analog of a pyrimidine
„
„
„
resembles Thymine (T)
has Br atom at C-5 instead of methyl
group as in T
can incorporate into DNA and pair with
either A or G due to tautomerization
5-Bromouracil
analog of a pyrimidine
* TAUTOMERIZATION – spontaneous structural alternations
between 2 forms, keto form and enol form
Mechanism of 5Bromouracil
Mechanism of 5Bromouracil
Chemical Mutagens-
Chemical modification agents
„
„
„
„
Chemicals which alter structure and
pairing properties of normal bases
Active on both replicating and nonreplicating DNA
Result in mutation upon DNA replication
by forming baseless sites or mispair
Two common chemical modification
agents
„
„
Alkylating agents
Deaminating agents
Alkylating agents
„
„
Modify the normal bases by adding
alkyl groups
Common alkylating agents
„
„
„
„
Ethylmethane sulfonate (EMS)
Nitrosoguanidine (NG)
Di-(2-chloroethyl) sulfide (Sulfur mustard)
Di-(2-chloroethyl) methylamine (Nitrogen
mustard)
Alkylating agents
Ethylmethane sulfonate (EMS)
Mechanism of
Ethylmethane sulfonate (EMS)
Ethylate base’s 7-N & 6-O positions
Mechanism of
Ethylmethane sulfonate (EMS)
Ethylate base’s 7-N & 6-O positions
Deaminating agents
„
Oxidative deamination of amino
group in Adenine (A), Guanine (G)
and Cytosine (C)
Deaminating agents
„
Nitrous acid (HNO2) is one of
common deaminating agents
„
„
Convert the amino group (-NH2) into keto
group (=O)
Change H-bonding potential of the
modified bases
Mechanism of Nitrous acid
Adenine (A) → Hydroxanthine
Mechanism of Nitrous acid
Cytosine (C) → Urail
Mechanism of Nitrous acid
Guanine (G) → Xanthine
Chemical MutagensIntercalating agents
„
„
„
A group of aromatic organic
molecules
Roughly the same dimensions as a
nitrogenous base pair
Intercalate or wedge between the
base pair
Chemical MutagensIntercalating agents
„
„
„
Cause addition or deletion of base
pairs of intact DNA
Alter reading frame of gene
Result in non-functional gene
product
Mechanism of
Intercalating agents
Mechanism of
Intercalating agents
„
Common intercalating agents
„
„
2,8-Diamino acridine (proflavin)
Acridine orange
Physical Mutagens
„
Ionising radiation
e.g. x rays, γrays,
cosmic rays
„
Non-ionising radiation
e.g. UV radiation
Ionizing Radiation
(high energy and penetrating)
„
Natural Sources:
Sunlight, outer space
„
Artificial Sources:
Medical diagnostic, powerplant
Ionizing Radiation
(high energy and penetrating)
„
Mechanism
„
„
Production of highly reactive free radicals
(OH• radicals)
Interaction between the radicals and DNA,
proteins, lipids in cell membrane etc.
Ionizing Radiation
(high energy and penetrating)
„
Effects
„
„
„
Organelle failure
Cell division blockage
Cell death
Interaction with DNA
„
Breaks in one or both strands
(can lead to rearrangements, deletions,
chromosome loss Æ death if unrepaired)
„
Damage to/loss of bases (mutation)
„
Crosslinking of DNA to itself or proteins
Interaction with DNA
normal sequence
CATTCACCTGTACCA
GTAAGTGGACATGGT
deletion
CATCACCTGTACCA
GTAGTGGACATGGT
Base pair mutation
Non-Ionizing Radiation
(Less energy, Non-penetrating)
Take UV radiation as an example
„ Its wavelengths are preferentially absorbed by
bases of DNA and by aromatic amino acids of
proteins
„
Normally classified in terms of its wavelengths:
UV-A, UV-B, UV-C (in decreasing order of
wavelengths)
Non-Ionizing Radiation
(Less energy, Non-penetrating)
„
Mechanism
„
Formation of Thymine dimers
„
These dimers cause the strand to buckle,
disrupting normal base pairing
„
Prevent normal replication and transcription
Formation of Thymine-thymine dimer
Biological Mutagens
„
Transposable element
„
Insertions result in dysfunction of genes
„
Common biological mutagens
„
„
„
Rubella virus
Cytomegalovirus
Hepatitis B virus
Biological Mutagens
Biological agents
Conclusion
„
Mutation
„
„
Mutagen
„
„
„
„
Spontaneous Mutation & Induced Mutation
Chemical Mutagens
Radiation
Biological Mutagens
Exposure to mutagen may induce mutation!
References
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Principles of Genetics
An Introduction of Genetic Analysis
DNA replication
http://pharmacology.unmc.edu/cancer/anti
bio.htm
Thank You
Chan Ho Yin, Aurora (02690763)
Chen Yiwei, Echo (01790443)
Co Ngai Na, Chloe (02715283)
Lam Kit Ming, Germaine (02770293)