Abundant lipophilic DNA adducts in human tissues

Lipophilic DNA adducts are a complex group of structurally unidentified DNA adducts present in human DNA which can be extracted to l-butanol and are w ell retained in C-18 columns during HPLC analysis. Levels of these lipophil ic adducts when determined by P-32-HPLC are high. Their abundance highlight s the importance of further study. In this study, the Lipophilic adducts we re analysed by P-32-HPLC in human lung, lymphocyte, breast, skin, colon and endometrial tissues. Tissue-specific patterns of the adducts were shown an d the adduct levels in these tissues were 9.7, 13.8, 8.9, 17.0, 1.8 and 2.3 x 10(-7), respectively. In order to find the possible sources of the Lipop hilic DNA adducts, effects of cigarette smoking, occupational exposure to P AHs, and age on adduct levels in lymphocytes were examined by analyzing sam ples 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 w orkers 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 w ere (13.7 +/- 4.7)/10(7) and (13.8 +/- 8.0)/10(7), respectively, not influe nced by age. But the levels of two major HPLC fractions in the elderly volu nteers 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), resp ectively). These results suggested a possible endogenous origin of some of the lipophilic DNA adducts. In further support of this speculation, by comp aring 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-hydroxynonena l, a major product of lipid peroxidation. (C) 1998 Elsevier Science B.V. AU rights reserved.