Environmental Carcinogens and Mutagens

Environmental agents (chemicals, radiation and viruses) can be carcinogens (cancer-causing substances) and mutagens (substances that alter DNA). The steps from mutagen/carcinogen to tumour involve mutagen/carcinogen activation by metabolism, reaction with DNA to give a DNA adduct and DNA replication of the adduct, resulting in a mutation; a mutation in a cancer gene may result in enhanced growth potential, and ultimately in tumour growth.

Keywords: mutations; cancer; environment; DNA; disease; chemicals; carcinogens; mutagens

Figure 1. The structures of several chemical carcinogens discussed in the text. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH); PAHs are found in soots and are produced by incomplete combustion (e.g. in exhaust gases from internal combustion engines and power plants, cigarette smoke and charred foods). Aflatoxin B1 (AFB1) is a mycotoxin produced by moulds that grow on improperly stored foodstuffs (e.g. peanuts). Two aromatic amines are shown: PhIP, found in charred foods; and benzidine, an industrial chemical. Two alkylating (methylating) agents are shown: dimethylnitrosamine (DMN), found in certain foods; and NNK, found in cigarette smoke.
Figure 2. The carcinogenesis paradigm, using benzo[a]pyrene as an example (see text). The horizontal arrows lead towards greater toxicity (in particular toward cancer), while the vertical arrows lead toward lesser toxicity.
close
 References
    book Balmain A, Brown R and Harris CC (eds) (2000) "Twentieth anniversary special issue [which contains reviews of various carcinogenesis topics]". Carcinogenesis 21: 339–531.
    Chaney SG and Sancar A (1996) DNA repair: enzymatic mechanisms and relevance to drug response. Journal of the National Cancer Institute 88: 1346–1360.
    Conney AH (1982) Induction of microsomal enzymes by foreign chemicals and carcinogens by polycyclic aromatic hydrocarbons. Cancer Research 42: 4875–4917.
    book Cooper GM (1995) Oncogenes, 2nd edn. London: Jones and Bartlett.
    Earnshaw WC, Martins LM and Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates and functions during apoptosis. Annual Review of Biochemistry 68: 383–424.
    book Eaton DL and Groopman JD (eds) (1994) The Toxicology of Aflatoxins. New York: Academic Press.
    book Friedberg EC, Walker GW and Seide W (1995) DNA Repair and Mutagenesis. Washington, DC: ASM Press.
    Greenblatt MS, Bennett WP, Hollstein M and Harris CC (1994) Perspectives in cancer research: mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Research 54: 4855–4878.
    Hainaut P, Hernandez T, Robinson A et al. (1998) IARC database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualization tools. Nucleic Acids Research 26: 205–213.
    book Hall J and Hainaut R (eds) (2000) "Reviews in mutation research". Mutation Research 462: 49–430.
    book Harvey RG (1997) Polycyclic Aromatic Hydrocarbons: Chemistry and Cancer. New York: Wiley-VCH.
    Hoffmann D and Hoffmann I (1997) The changing cigarette, 1950–1995. Journal of Toxicology and Environmental Health 50: 307–364.
    book Kitchen KT (1998) Carcinogenicity: Testing, Predicting and Interpreting Chemical Effects. New York: Marcel Dekker.
    book Loechler EL (1994) "Mechanism by which aflatoxins and other bulky carcinogens induce mutations". In: Eaton DL and Groopman JD (eds) The Toxicology of Aflatoxins: Human Health, Veterinary, and Agricultural Significance, pp. 149–178. Orlando, FL: Academic Press.
    book Loechler EL, Henry B and Seo K-Y (2000) "Biological responses to chemical carcinogens". In: The Molecular Basis of Human Cancer. Totowa, NJ: Humana Press.
    Miller JH (1983) Mutational specificity in bacteria. Annual Review of Genetics 17: 215–238.
    book Nickoloff JA and Hoekstra MF (eds) (1998) DNA Damage and Repair, vols. 1 and 2. Totowa, NJ: Humana Press.
    Nurse P (2000) A long twentieth century of the cell cycle and beyond. Cell 2000: 71–78.
    book Searle CE (ed.) (1984) Chemical Carcinogens, 2nd edn, "ACS Monograph 182". Washington DC: American Chemical Society.
    Selikoff I and Hammond EC (1978) Asbestos-associated diseases in the United States shipyards. Cancer 28: 67–99.
    book Singer B and Grunberger D (1983) Molecular Biology of Mutagens and Carcinogens. New York: Plenum Press.
    book Stein GS, Baserga R, Giordano A and Denhardt DT (eds) (1999) The Molecular Basis of Cell Cycle and Growth Control. New York: Wiley-Liss.
    book Varmus H and Weinberg RA (1993) Genes and the Biology of Cancer. New York: Scientific American Library.
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Loechler, Edward L(Jan 2003) Environmental Carcinogens and Mutagens. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001477]