Abundant lipophilic DNA adducts in human tissues

Abstract

Lipophilic DNA adducts are a complex group of structurally unidentified DNA adducts present in human DNA which can be extracted to 1-butanol and are well retained in C-18 columns during HPLC analysis. Levels of these lipophilic adducts when determined by 32 P-HPLC are high. Their abundance highlights the importance of further study. In this study, the lipophilic adducts were analysed by 32 P-HPLC in human lung, lymphocyte, breast, skin, colon and endometrial tissues. Tissue-specific patterns of the adducts were shown and the adduct levels in these tissues were 9.7, 13.8, 8.9, 17.0, 1.8 and 2.3×10 −7, respectively. In order to find the possible sources of the lipophilic DNA adducts, effects of cigarette smoking, occupational exposure to PAHs, and age on adduct levels in lymphocytes were examined by analyzing samples collected from 20 Swedish elderly volunteers with a mean age of 55 (10 smokers and 10 non-smokers) and 20 Swedish younger aluminium and control workers with a mean age of 39. Exposures to cigarette smoke and PAHs did not increase total adduct levels nor the levels of major, individual adducts. The total adduct levels in the elderly volunteers and the younger workers were (13.7±4.7)/10 7 and (13.8±8.0)/10 7, respectively, not influenced by age. But the levels of two major HPLC fractions in the elderly volunteers differed significantly from those in the younger workers (25.1/10 8 vs. 8.7/10 8 ( P<0.0001), and 15.4/10 8 vs. 28.5/10 8 ( P<0.01), respectively). These results suggested a possible endogenous origin of some of the lipophilic DNA adducts. In further support of this speculation, by comparing migration properties in HPLC and TLC of human adducts with a standard, we found an adduct in human lung tissue that was putatively induced by 2,3-epoxy-4-hydroxynonanal which is an epoxidation product of 4-hydroxynonenal, a major product of lipid peroxidation.