DNA adducts and human atherosclerotic lesions

It has been hypothesized that mutational events may be involved in the athe rogenetic process and that at least a portion of atherosclerotic plaques ma y be the results of monoclonal proliferation of a single mutated smooth mus cle cell (SMC). Therefore, atherosclerosis may be similar to carcinogenesis and may have an environmental etiology. We have analyzed bulky-aromatic DN A adducts in human thoracic aortas from mate subjects, aged between 30-60 y ears, who died suddenly or accidentally, and who had been examined by autop sy within 24 h after death. We found significantly (P < 0.001) higher DNA a dduct levels in the samples from subjects with frequent atherosclerotic cha nges in the whole body ("Cases", N = 76) compared with those having few ath erosclerotic changes ("Controls", N = 57). We also observed a significantly elevated weight of heart and plasma levels of total and LDL cholesterol in "Cases" vs "Controls". Significant differences in DNA adduct levels betwee n smokers and nonsmokers were observed in "Controls" only. Multivariate lin ear regression analyses with age-adjusted data confirmed a significant infl uence of LDL cholesterol (P < 0.001), vitamin A (P < 0.01), smoking behavio r (P < 0.05; evaluated as plasma cotinine levels) and NAT2 genotypes (P < 0 .05) on bulky-aromatic DNA adduct levels. The induction of DNA adducts sugg ests that alterations at the DNA level may contribute to the development of atherosclerosis. Furthermore, atherogenesis and carcinogenesis may share a similar etiology, i.e. genotoxic action of environmental chemicals.