DETERMINATION OF DNA-ADDUCTS OF MALONALDEHYDE IN HUMANS - EFFECTS OF DIETARY FATTY-ACID COMPOSITION

The effects of dietary fatty acid composition on the endogenous format ion of DNA adducts of malonaldehyde (MA), the major product of lipid p eroxidation, were investigated in humans, A group of 59 healthy indivi duals of both sexes and different ages was initially fed a milk fat-ba sed diet rich in saturated fatty acids for 14 days, Following this ini tial period, after which the group was considered homogeneous with res pect to diet, 30 randomly chosen subjects were given a sunflower oil-b ased (rich in polyunsaturated fatty acids) (SO) diet and the remaining 29 individuals a low erucic acid rapeseed oil-based (rich in monounsa turated 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 di etary periods, DNA adduct levels were measured by P-32-post-labelling using reversed-phase HPLC with on-line detection of radioactivity, Hig her concentrations of polyunsaturated fatty acids in plasma triglyceri des 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 lar ge inter-individual variation in adduct levels was observed, The avera ge adduct level in the SO diet group was 7.4 +/- 8.7 adducts/10(7) nuc leotides (n = 23), This level was 3.6-fold higher than that found in i ndividuals in the RO diet group (P < 0.001), Our results, in conjuncti on with the mutagenic and carcinogenic properties of MA, thus suggest the interaction of lipid peroxidation products such as MA with DNA as one pausible mechanism explaining the involvement of dietary fat in ca rcinogenesis.