Influence of CYP1A2 and NAT2 metabolic phenotypes on smokers urinary mutagenicity

The influence of the metabolic phenotypes NAT2 and CYP1A2 on urinary mutagenicity of 118 smokers was studied. Mutagenicity of urine samples was determined by Ames test (preincubation plate incorporation assay on YG1024 Salmonella typhimurium strain with S9 mix). Urinary nicotine plus its metabolites were determined to check cigarette smoke intake. The N-acetyltransferase (NAT2) and cytochrome P450 1A2 (CYP1A2) phenotypes were measured by the molar ratio of urinary caffeine metabolites, determined by HPLC analysis. Urinary mutagenicity was significantly higher in smokers CYP1A2 extensive (EM) than in CYP1A2 poor metabolizers (PM) (Mann-Whitney U test, p = 0.020). Linear multiple regression analysis shows that an increase in urinary mutagenicity levels was significantly related to cigarette smoke intake and to CYP1A2 N-hydroxylation activity (t = 5.06, p < 0.001, and t = 2.33, p = 0.021), but not to NAT2 acetylation phenotype. In conclusion, phenotypic differences in metabolic activation of tobacco smoke mutagens are able to modulate the presence of mutagens in urine of cigarette smokers and, consequently, the potential genotoxic risk.