Comparison of DNA adduct levels associated with exogenous and endogenous exposures in human pancreas in relation to metabolic genotype

Recently, we examined normal human pancreas tissue for DNA adducts derived from either exogenous chemical exposure and/or endogenous agents. In an eff ort to explain the different types and levels of DNA adducts formed in the context of individual susceptibility to cancer, we have focused on gene-env ironment interactions. Here, we report on the levels of hydrophobic aromati c amines (AAs), specifically those derived from 4-aminobiphenyl (ABP), and DNA adducts associated with oxidative stress in human pancreas. Although th ese adducts have been reported in several human tissues by different labora tories, a comparison of the levels of these adducts in the same tissue samp les has not been performed. Using the same DNA, the genotypes were determin ed for N-acetyltransferase 1 (NAT1), the glutathione S-transferase (GST) M1 , GSTP1, GSTT1, and NAD(P)H quinone reductase-1 (NQO(1)) as possible modula tors of adduct levels because their gene products are involved in the detox ification of AAs, lipid peroxidation products and in redox cycling. These r esults indicate that ABP-DNA adducts, malondialdehyde-DNA adducts, and 8-ox o-2'-deoxyguanosine (8-oxo-dG) adducts are present at similar levels. Of th e metabolic genotypes examined, the presence of ABP-DNA adducts was strongl y associated with the putative slow NAT1*4/*4 genotype, suggesting a role f or this pathway in ABP detoxification. (C) 1999 Elsevier Science B.V. All r ights reserved.