Abstract
THE metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined1,2. Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust3,4. We have determined levels of DNA adducts in bladder cells and of 4-aminobipheny7l–haemo-globin adducts in 97 volunteers, together with the N-acetylation non-inducible phenotype, the corresponding genotype, and the levels of nicotine–cotinine in the urine. We find that among the slow acetylators, 4-aminobiphenyl adducts were higher than in rapid acetylators at low or null nicotine–cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing nicotine–cotinine levels. The N-acetyltransferase genotype is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to ‘risk assessment’ procedures.
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Vineis, P., Bartsch, H., Caporaso, N. et al. Genetically based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens. Nature 369, 154–156 (1994). https://doi.org/10.1038/369154a0
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DOI: https://doi.org/10.1038/369154a0
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