Aflatoxin-DNA adducts as biomarkers of cancer: Nature, formation, kinds of AF-DNA adducts, methodology, effects, and control
Por:
Carvajal M.
Publicada:
1 ene 2008
Categoría:
Chemistry (miscellaneous)
Resumen:
Aflatoxins (AF) are potent carcinogens of foods, and the exposure of humans to them is continuous. Aflatoxin-DNA adduct's nature, chemical reactions, and molecular biology are of primary importance because they are the source of mutagenicity and risk of cancer in animals and humans. The measurement of aflatoxin-DNA adducts as biomarkers of long-term risk of disease in people, their proper assessment and the quantification of these active carcinogens is of great importance, because these adducts are directly related to the AF damaging effects and can explain the origin of the cancer under study. Relatively few biomarkers of long-term health have been even partially validated in experimental animals and in people. AF activates in the presence of the cytochrome P450, as an unstable molecule called AF 8,9-epoxide; later this compound links mainly to the N7 of the guanine nucleotide forming an adduct which is the active carcinogen itself and behaves as a biomarker, that is to say an objective measure of human exposure to environmental carcinogens. Adducts represent an integration of exposure, absorption, distribution, metabolism, DNA repair, and cell turnover, and thus provide a measure of biologically effective dose. The different issues presented in this chapter are: 1) Factors related to AFB-DNA adduct formation: age, cigarette smoking, alcohol drinking, organ susceptibility to form adducts (e.g., liver parenchymal cells, lung tissue, small intestine, tracheal explant cultures, placenta, bile radical intermediates, etc.), and temperature modulation of AFB1 hepatic metabolism; 2) In vitro and in vivo studies of AFB1-DNA adduct formation primarily at the N7 position of guanine; 3) Formation of AFB 2 adducts; 4) Dietary AFB1 exposure, development of human primary hepatocellular carcinoma (HCC) and mutations in the p53 tumor suppressor gene. The effect of diet in the adduct formation (choline-deficient/low methionine diet, food and caloric restriction, and the role of enzymes); 5) Routes of exposure for DNA adduct formation; 6) Vitamins; 7) Kinds of AF-DNA adducts (guanine, formamidopyrimidine), protein adducts (hemoglobin, albumin) and lysine, adenosine and cytosine AFB1 adducts; 8) Methodology: a. reversed-phase high-pressure liquid chromatography (LC), b. a liquid chromatography electrospray
Filiaciones:
Carvajal M.:
Departamento de Botánica, Instituto de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México, D.F., Mexico
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