GENETICALLY BASED N-ACETYLTRANSFERASE METABOLIC POLYMORPHISM AND LOW-LEVEL ENVIRONMENTAL EXPOSURE TO CARCINOGENS

THE metabolic activation or inactivation of carcinogens varies conside rably in human populations, and is partly genetically determined(1,2). Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. E xamples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust(3,4). We have determined levels of DNA adducts in bladder cells and of 4-amino biphenyl-haemoglobin adducts in 97 volunteers, together with the N-ace tylation 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 acetyla tors at low or null nicotine-cotinine levels, whereas the difference b etween slow and rapid acetylators was less evident at increasing nicot ine-cotinine levels. The N-acetyltransferase genotype is highly predic tive of the acetylation phenotype. Our results indicate that the clear ance of low-dose carcinogens is decreased in the genetically based slo w-acetylator phenotype. Such genetic modulation of low-dose environmen tal risks is relevant to 'risk assessment' procedures.