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The effect of alcohol drinking on the formation of DNA adducts of acetaldehyde, the primary oxidative metabolite of ethanol, was investigated in humans. DNA was isolated from granulocytes and lymphocytes from 24 alcoholic patients and 12 control subjects. DNA adduct levels were measured by 32P-postlabelling using reversed-phase HPLC with on-line detection of radioactivity. A large interindividual variation in adduct levels was observed. The average adduct levels in granulocyte and lymphocyte DNA from alcoholic patients were 3.4 +/- 3.8 and 2.1 +/- 0.8 adducts/10(7) nucleotides (n = 24), respectively. These levels were 13- and 7-fold higher than the corresponding levels in control subjects (P<0.001). The average adduct level in granulocyte DNA from alcoholic patients was 60% higher than in lymphocyte DNA (P<0.01). Our results, in conjunction with the genotoxicity of acetaldehyde, thus suggest the formation of DNA adducts of acetaldehyde as a plausible mechanism explaining the involvement of alcohol drinking in carcinogenesis.

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The effects of dietary fatty acid composition on the endogenous formation of DNA adducts of malonaldehyde (MA), the major product of lipid peroxidation, were investigated in humans. A group of 59 healthy individuals of both sexes and different ages was initially fed a milk fat-based diet rich in saturated fatty acids for 14 days. Following this initial period, after which the group was considered homogeneous with respect to diet, 30 randomly chosen subjects were given a sunflower oil-based (rich in polyunsaturated fatty acids) (SO) diet and the remaining 29 individuals a low erucic acid rapeseed oil-based (rich in monounsaturated fatty acids) (RO) diet for 25 days. The fatty acid composition of plasma lipid fractions and the level of DNA adducts of MA in total white blood cells were then determined at the end of the SO and RO dietary periods. DNA adduct levels were measured by 32p-postlabelling using reversed-phase HPLC with on-line detection of radioactivity. Higher concentrations of polyunsaturated fatty acids in plasma triglycerides and higher levels of DNA adducts of MA were found in the subjects on the SO diet when compared with those in the RO dietary group. A large inter-individual variation in adduct levels was observed. The average adduct level in the SO diet group was 7.4 +/- 8.7 adducts/10(7) nucleotides (n = 23). This level was 3.6-fold higher than that found in individuals in the RO diet group (P < 0.001). Our results, in conjunction with the mutagenic and carcinogenic properties of MA, thus suggest the interaction of lipid peroxidation products such as MA with DNA as one plausible mechanism explaining the involvement of dietary fat in carcinogenesis.