ACIDIC URINE PH IS ASSOCIATED WITH ELEVATED LEVELS OF FREE URINARY BENZIDINE AND N-ACETYLBENZIDINE AND UROTHELIAL CELL-DNA ADDUCTS IN EXPOSED WORKERS

We evaluated the influence of urine pH on the proportion of urinary be nzidine (BZ) and N-acetylbenzidine present in the free, unconjugated s tate and on exfoliated urothelial cell DNA adduct levels in 32 workers exposed to BZ in India, Postworkshift urine pH was inversely correlat ed with the proportions of BZ (r = -0.78; P < 0.0001) and N-acetylbenz idine (r = -0.67; P < 0.0001) present as free compounds, Furthermore, the average of each subject's pre-and postworkshift urine pH was negat ively associated with the predominant urothelial DNA adduct (P = 0.003 7, adjusted for urinary BZ and metabolites), which has been shown to c ochromatograph with a N-(3'-phosphodeoxyguanosin-8-yl)-N'acetylbenzidi ne adduct standard, Controlling for internal dose, individuals,vith ur ine pH <6 had 10-fold higher DNA adduct levels compared to subjects wi th urine pH greater than or equal to 7. As reported previously, polymo rphisms in NAT1, NAT2, and GSTM1 had no impact on DNA adduct levels, T his is the first study to demonstrate that urine pH has a strong influ ence on the presence of free urinary aromatic amine compounds and on u rothelial cell DNA adduct levels in exposed humans, Because there is e vidence that acidic urine has a similar influence on aromatic amines d erived from cigarette smoke, urine pH, which is influenced by diet, ma y be an important susceptibility factor for bladder cancer caused by t obacco in the general population.