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Carcinogens Chart, 2012 ACMT Board Review Course Handout Antineoplastic drugs Group 1 Agent Busulfan Chlorambucil Cyclophosphamide Melphalan Semustine (methyl CCNU) Thiotepa Treosulfan MOPP combined therapy Etoposide in combo with cisplatin and bleomycin Etoposide Cancer site Acute myeloid Acute myeloid Acute myeloid bladder Acute myeloid Acute myeloid Leukemia Acute myeloid Acute myeloid Acute myeloid leukemia leukemia leukemia, leukemia leukemia leukemia leukemia leukemia Chlomphazine Bladder Azathioprine Cyclosporin Methoxsalen + UV light Non-Hodgkin lymphoma, skin Non-Hodgkin lymphoma, skin, multiple other sites Skin Plants with aristolochic acid Renal pelvis, ureter Aristolochic acid Analgesic mixtures containing phenacetin Phenacetin Renal pelvis, ureter Prepared by Christine Murphy, MD Established mechanistic events Genotoxicity (alkylating agent) Genotoxicity (alkylating agent) Genotoxicity (metabolism to alkylating agent) Genotoxicity (alkylating agent) Genotoxicity (alkylating agent) Genotoxicity (alkylating agent) Genotoxicity (alkylating agent) Genotoxicity (alkylating agent) Genotoxicity; translocation involving MLL gene (etoposide) Genotoxicity; translocation involving MLL gene Genotoxicity (alkylating agent, metabolism to 2-naphthylamine derivatives) Genotoxicity, immunosuppression Immunosuppression Genotoxicity following photoactivation Genotoxicity; DNA adducts in humans A:T to T:A transversion in TP53 in human tumors Genotoxicty; DNA adducts in animals animals are the same as those found in humans exposed to plants, A:T to T:A transversions in TP53, RAS activation (see below) Genotoxicity, cell proliferation Carcinogens Chart, 2012 ACMT Board Review Course Handout Hormonal Treatments Group 1 agent Cancer site Est. mechanism Diethylstilbestrol Breast (user) Vagina/cervix (in utero exp) Testicular (in utero exp) Estrogen-only menopausal therapy Combined estrogenprogestogen menopausal therapy Combined estrogenprogestogen oral contraceptives Endometrium, ovary Estrogen receptor mediated events (vagina/cervix); genotoxicity Estrogen receptor mediated events Receptor-mediated events Tamoxifen Endometrium (breast DECREASED) Endometrium (risk of diseases with number of days/months of progestrogen);breast Breast, cervix, liver (endometrium and ovary DECREASED) Receptor-mediated events Other likely mechanisms Epigenetic programming Genotoxicity Estrogen genotoxicity Estrogen genotoxicity, hormone-stimulated expression of humanpapilloma virus genes Estrogen receptormediated events, genotoxicity Personal health Agent Tobacco smoking Parenteral smoking (cancer in offspring) Second hand smoke Smokeless tobacco Betel quid with tobacco Betel quid without tobacco Alcohol consumption Acetylaldehyde associated with alcohol consumption Chinese style salted fish Indoor emissions from household combustion of coal Prepared by Christine Murphy, MD Tumor sites Oral cavity, oropharynx Nasopharynx, hypopharynx Esophagus (adenocarcinoma & squamous cell) Stomach, colorectum Liver, pancreas Nasal cavity and paranasal sinuses Larynx, lung Uterine, cervix, ovary (mucinous) Urinary bladder, kidney (body and pelvis) Ureter, bone marrow (myeloid leukemia) Hepatoblastoma Lung Oral cavity, esophagus, pancreas Oral cavity, pharynx, esophagus Oral cavity, esophagus Oral cavity, pharynx, larynx, esophagus, liver, colorectum, female breast Esophagus, head and neck Nasopharynx Lung Carcinogens Chart, 2012 ACMT Board Review Course Handout Chemicals Agent Aromatic amines 4-Aminobiphenyl Benzidine Dyes metabolized to benzidine 4,4’methylenebis(2chloroaniline) 2-Naphthylamine Ortho-toluidine Auramine production Magenta production PAH-related exposures Benzo(a)pyrene Soot (chimney sweeps) Coal gasification Coal-tar distillation Coke production Coal-tar pitches (paving,roofing) Aluminum production Other chemicals Aflatoxins Benzene Bis(chloromethyl)ether/ Chloromethylmethylether 1,3-Butadiene Dioxin (2,3,7,8 TCDD) 2,3,7,8Pentachlordibenzofuran 3,3’,4,4’,5-Pentachlrobiphenyl (PCB-126) Ethylene oxide Formaldehyde Sulfur mustard Vinyl chloride Other complex exposures Iron and steel founding Isopropyl alcohol manufacture using strong acids Mineral oils Occupational exposure as a painter Rubber manufacturing industry Shale oils Strong inorganic acid mists Tumor site Evidence that genotoxicity is main mechanism Urinary bladder Urinary bladder Strong Strong Strong Strong Urinary Urinary Urinary Urinary bladder bladder bladder bladder Strong Moderate Weak/lack of data Weak/lack of data Skin, lung Lung Skin Lung Lung Strong Moderate Strong Strong Strong Strong Lung, urinary bladder Weak/moderate Hepatocellular carcinoma Acute non-lymphocytic leukemia Lung Strong Strong Haematolymphatic organs All cancers combined Strong Strong for aryl hydrocarbon receptor mediated mechanism (AhR) Strong (AhR) Moderate/strong Strong (AhR) Leukemia Nasopharynx Leukemia (myeloid) Lung Hepatic angiosarcoma Hepatocellular carcinoma Strong Strong Moderate Strong Strong Lung Nasal cavity Strong Moderate Skin Lung, urinary bladder, pleural mesothelioma Leukemia, lymphoma, urinary bladder, lung, stomach Skin Larynx Strong Strong Prepared by Christine Murphy, MD Strong Weak/lack of data Weak/lack of data Carcinogens Chart, 2012 ACMT Board Review Course Handout Metals, arsenic dust and fibers Agent Tumor site Arsenic and inorganic arsenic compounds Lung, skin, urinary bladder Beryllium and beryllium compounds Cadmium and cadmium compounds Lung Chromium (VI) compounds Lung Nickel compounds Lung, nasal cavity and paranasal sinuses Asbestos (chrysotile, crocidolite, amosite, tremolite, actinolite, anthrophyllite) Lung, mesothelioma, larynx, ovary Erionite Mesothelioma Silica dust, crystalline in the form of quartz or crystabalite Lung Leather dust Nasal cavity and paranasal sinuses Nasal cavity and paranasal sinuses, nasopharynx Wood dust Lung Prepared by Christine Murphy, MD Established mechanism of events Oxidative DNA damage, genomic instability, aneuploidy, gene amplification, epigenetic effects, DNA-repair inhibition leading to mutagenesis Chromosome aberrations, aneuploidy, DNA damage DNA-repair inhibition, disturbance of tumorsuppressor proteins leading to genomic instability Direct DNA damage after intracellular reduction to Cr(III), mutation, genomic instability, aneuploidy, cell transformation DNA damage, chromosome aberrations, genomic instability, micronuclei, DNArepair inhibition, alteration of DNA, methylation, histone modification Impaired fiber clearance leading to macrophage activation, inflammation, generation of reactive oxygen and nitrogen species, tissue injury, genotoxicity, aneuploidy and polyploidy, epigenetic alteration, activation of signaling pathways, resistance to apoptosis Genotoxicity Impaired particle clearance leading to macrophage activation and persistent inflammation Carcinogens Chart, 2012 ACMT Board Review Course Handout Radiation Radiation type Radon 222 and decay Tumor sites Lung Radium 224 and decay Radium 226, radium 228 and decay Throium 232 and decay Bone Bone, paranasal sinuses Mastoid process (radium 226 only) Liver, extrahepatic biliary ducts Gall bladder Leukemia (excluding CLL) Lung, liver, bone Acute leukemia Solid cancers, leukemia Plutonium Phosphorous 32 Fission products, including strontium 90 Radioiodines, including iodine 131 OTHER X-radiation or gamma radiation Solar radiation UV emitting tanning devices Thyroid Salivary gland, esophagus Stomach, colon Lung, bone Skin (BCC) Female breast Urinary bladder Brain & CNS Leukemia (excluding CLL) Thyroid Kidney (atomic bomb survivors/medical pts) Multiple sites (in utero exp) Skin (BCC, SCC, melanoma) Skin (melanoma) Eye (melanoma, particularly choroid & ciliary body) Prepared by Christine Murphy, MD Major study populations General pop (residential exp) Underground miners Medical patients Radium-dial painters Medical patients Plutonium-production workers Medical patients Gen pop following nuclear reactor accident Children and adolescents following nuclear reactor accidents Atomic bomb survivors Medical patients In-utero exposure offspring of pregnant medical patients and of atomic bomb survivors. General population General population Carcinogens Chart, 2012 ACMT Board Review Course Handout Biological agents Agent Cancer site Epstein Barr Virus Nasopharyngeal carcinoma Burkitt’s lymphoma Extranodal NK/T-cell lymphoma (nasal type) Hodgkin’s lymphoma Hepatocellular carcinoma Hepatitis B Virus Hepatitis C Virus Kaposi’s sarcoma herpes virus HIV 1 HPV 16 Human T cell lymphotrophic virus, type1 Heliobacter pylori Hepatocellular carcinoma Non-Hodgkin’s lymphoma Kaposi’s sarcoma Primary effusion lymphoma Kaposi’s sarcoma Non-hodgkin’s lymphoma Hodgkin’s lymphoma Cancer of cervix, anus, conjunctiva Cervix, vagina, vulva Penis, anus OP, tonsil, oral cavity Adult T-cell leukemia & lymphoma Clonorchis sinemsis Opsithochis viverrini Non-cardia gastric carcinoma Low-grade B cell associated lymphoid tissue (MALT) Gastric lymphoma Cholangiosarcoma Cholangiosarcoma Schistosoma haemetobium Urinary bladder Prepared by Christine Murphy, MD Established mechanism of events Cell proliferation, inhibition of apoptosis, genomic instability, cell migration Inflammation, liver cirrhosis, chronic hepatitis Inflammation, liver cirrhosis, liver fibrosis Cell proliferation, inhibition of apoptosis, genomic instability, cell migration Immunosuppression (indirect action) Immortalization, genomic instability, inhibition of DNA damage response, antiapoptotic activity Immortalization and transformation of T-cells Inflammation, oxidative stress, altered cellular turnover and gene expression, methylation mutation Inflammation, oxidative stress, cell-proliferation Inflammation, oxidative stress
