Chemical carcinogenesis

About 80% of human tumors are caused by environmental factors, especially chemicals. Exposure to these compounds occurs due to:
 * employment (e.g. benzene, asbestos…)
 * diet (e.g. aflatoxin B1, which is produced by the fungus Aspergillus flavus and is occasionally found as a contamination of peanuts and other foods; furthermore, the most risky foods include animal fats and foods containing them; inappropriate food preparation - frying, baking, smoking, etc., which increases the content of carcinogenic substances)
 * lifestyle (smoking cigarettes…)

Classification of chemical carcinogens

 * 1) primary carcinogens: active without metabolic activation
 * 2) secondary carcinogens: at first they must be activated by biotransformation → procarcinogens
 * 3) carcinogens: directly increase the carcinogenic effect (by inducing biotransformation enzymes)
 * 4) promoters: indirectly increase the carcinogenic effect by stimulating proliferation

Procarcinogens
náhled|Mechanismus chemické kancerogeneze


 * metabolic activation to ultimate carcinogens catalyzed by one or more enzymes is required =&gt; possible sequence: procarcinogen – intermediate carcinogen – final carcinogen
 * metabolism of chemical carcinogenesis: metabolism procarcinogens and other xenobiotics includes monooxygenases a transferases – enzymes responsible for the metabolic activation of procarcinogens are part of the system cytochrom P-450 in endoplasmic reticulum. Their activity is influenced by a number of factors, such as species influences, genetic factors, age or gender
 * oespecially monooxygenase involved in the metabolism of polycyclic aromatic [[hydrocarbons] (playing an important role in chemical carcinogenesis) is often called cytochrome P-448 or hydroxylase of aromatic hydrocarbons


 * 1) polycyclic aromatic hydrocarbons – PAH – benzanthracene (1. pure carcinogen) – 3,4-benzopyrene (from coal tar) – 3-methylcholanthrene (prepared from steroids, deoxycholic acid) – 7,12-dimethylbenzanthracene (the most effective carcinogen)
 * 2) aromatic amines and azo dyes– 2-naftylamine (causes bladder cancer) – 2-acetylaminofluorene – 4-dimethylaminoazobenzene (causes hepatomas)
 * 3) natural substances – products of fungi and plants – aflatoxin B1 (hepatokarcinogen, food contamination, causes mutations in DNA, G → T conversion in the p53 molecule, HBV is a synergistic factor in the carcinogenesis of aflatoxin B1) – mitomycin C-cytostatic
 * 4) others – nitrosamines (can be formed by the action of bacteria on nitrites in food) – insecticides (chlordane) – tetrachlormethane – ethylene oxide – some metals

Direct carcinogens

 * they react directly with DNA
 * 1) alkylating agents – cytostatics and immunosuppressants – beta-propiolaktone – bis-chloromethyl ether
 * 2) acetylating agents – 1-acetylimidazole

Other possible divisions of chemicals with mutagenic effect

 * 1) substances that induce mutations only during replication (= base analogues (5-bromouracil – zcauses base mismatches) and acridine dyes (acridine orange - induces reading frame shift))
 * 2) substances that are mutagenic in action on non-replicating DNA (substances causing alkylation (sulfur mustard – alkyl group donor), deamination (nitrous acid and nitrites), hydroxylation (hydroxyamine))

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Related articles

 * Physical carcinogenesis
 * Viral carcinogenesis