Metabolic activation of procarcinogens and cancer risk

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l. Ten strains of Salmonella typhimurium YG7108 expressing each form of human cytochrome P450 (CYP), CYP1A1, CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5, together with human NADPH-cytochrome P450 reductase (OR) have been established.2. Mutagens were formed from promutagens such as aflatoxin B_1 and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone bv human CYP forms expressed in the established Salmonella cells.3. 2-Phenylbenzotriazole derivatives, newly isolated from river water, are promutagens, were found to be activated by human CYP1A1 specifically.4. Individuals carrying a whole deletion genotype of the CYP2A6 gene showed significantly less lung cancer risk.5. Furthermore, it was found that the whole deletion of the CYP2A6 gene resulted in the low risk of small cell lung cancer and squamous cell lung cancer, which have been known to be caused associated with tobacco smoke.