DNA adducts and human atherosclerotic lesions.
It has been hypothesized that mutational events may be involved in the atherogenetic process and that at least a portion of atherosclerotic plaques may be the results of monoclonal proliferation of a single mutated smooth muscle cell (SMC). Therefore, atherosclerosis may be similar to carcinogenesis and may have an environmental etiology. We have analyzed bulky-aromatic DNA adducts in human thoracic aortas from male subjects, aged between 30-60 years, who died suddenly or accidentally, and who had been examined by autopsy within 24 h after death. We found significantly (P < 0.001) higher DNA adduct levels in the samples from subjects with frequent atherosclerotic changes in the whole body ("Cases", N = 76) compared with those having few atherosclerotic 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 between smokers and nonsmokers were observed in "Controls" only. Multivariate linear regression analyses with age-adjusted data confirmed a significant influence of LDL cholesterol (P < 0.001), vitamin A (P < 0.01), smoking behavior (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 suggests 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.
Binková
B
B
Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. bbinkova@biomed.cas.cz
Strejc
P
P
Boubelík
O
O
Stávková
Z
Z
Chvátalová
I
I
Srám
R J
RJ
D000328:Adult; D000367:Age Factors; D001013:Aorta, Thoracic / Q000473:pathology*; D001161:Arteriosclerosis / Q000235:genetics* / Q000503:physiopathology*; D001344:Autopsy; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood; D018736:DNA Adducts; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D008078:Cholesterol, LDL; D018736:DNA Adducts