MODULATION OF URINARY MUTAGENICITY BY GENETICALLY-DETERMINED CARCINOGEN METABOLISM IN SMOKERS

We examined the genotypes of two polymorphic genes involved in the det oxification of several mutagenic and carcinogenic compounds in relatio n to tobacco smoking-associated urinary mutagenicity. The genes studie d were the glutathione S-transferase-encoding GSTM1 gene and acetyltra nsferase-encoding NAT2 gene. Smokers with no GSTM1 gene (n = 7) had ur ine that was several times more mutagenic than that of smokers with th e gene (n = 10). The mean level of urinary mutagenicity in presence of metabolic activation was 2527 +/- 958 revertants/100 ml urine for GST M1- smokers compared to 766 +/- 560 revertants/100 ml for GSTM1+ smoke rs (P < 0.001) using the bacterial strain YG1024. The corresponding va lues using the TA98 strain were 336 +/- 124 and 123 +/- 75 (P < 0.001) . In contrast, we failed to show any difference in the level of urinar y mutagenicity between slow-acetylator and fast-acetylator NAT2 genoty pes among smokers (n = 17) or non-smokers (n = 35). Our results offer one explanation for the recent findings that GSTM1 polymorphism is a r isk modifier in smoking-related cancers, especially bladder cancer.