The adduct and the addict
The results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype, which is relevant to 'risk assessment' procedures.
Abstract
The metabolic activation or inactivation of carcinogens varies considerably in human populations and is partly genetically determined. 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 exhaust. We have determined levels of DNA adducts in bladder cells from 39 people and of 4—aminobiphenyl-haemoglobin 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 amongst slow acetylators, 4—aminobiphenyl-haemoglobin adducts were higher than in rapid acetylators at low or null cotinine-nicotine levels, whereas the difference between rapid and slow 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.