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• W1977632395 abstract "Atherosclerosis and cancer are characterized by uncontrolled cell proliferation and share common risk factors, such as cigarette smoking, dietary habits and ageing. Growth of smooth muscle cells (SMCs) in atherosclerotic plaques may result from DNA damage, caused either by exogenous mutagens or by agents endogenously generated due to oxidative stress and lipid peroxidation (LPO). Hydroxy-2-nonenal (HNE), a major LPO product, binds covalently to cellular DNA to form the exocyclic etheno-DNA-base adducts, 1,N6-ethenodeoxyadenine (ɛdA) and 3,N4-ethenodeoxycytosine (ɛdC). By applying an ultrasensitive 32P-postlabeling-immunoaffinity method, ɛdA and ɛdC were quantified in abdominal aorta SMCs from 13 atherosclerotic patients and 3 non-smoking subjects without atherosclerotic lesions. The levels of etheno-adducts ranged for ɛdA from 2.3 to 39.6/108 dA and for ɛdC from 10.7 to 157.7/108 dC, with a high correlation between ɛdA and ɛdC (r = 0.84, P = 0.0001). Etheno-adduct levels were higher in atherosclerotic smokers than in ex-smokers for both ɛdA (means 15.2 versus 7.3, P = 0.06) and ɛdC (71.9 versus 51.6, not significant). ɛdC levels were higher in either ex-smokers (P = 0.03) or smokers (P = 0.07) than in non-smokers. There was a poor correlation between either ɛdA or ɛdC and 8-hydroxy-2′-deoxyguanosine, whereas significant positive correlations were detected with the levels of several postlabeled bulky aromatic DNA adducts. In conclusion, two different types of DNA damage may be involved in atherosclerotic plaque formation and progression: (i) bulky aromatic compounds, to which aorta SMCs are chronically exposed in smokers, can either covalently bind to DNA, induce redox-cycling via quinone intermediates and/or activate local chronic inflammatory processes in the arterial wall; ii) this in turn leads to a self perpetuating generation of reactive oxygen species, LPO-products and increasing DNA-damage, as documented by the presence of high levels of miscoding etheno-DNA adducts in human aorta SMCs." @default.
• W1977632395 created "2016-06-24" @default.
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• W1977632395 date "2007-08-01" @default.
• W1977632395 modified "2023-10-17" @default.
• W1977632395 title "Lipid peroxidation-derived etheno-DNA adducts in human atherosclerotic lesions" @default.
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• W1977632395 doi "https://doi.org/10.1016/j.mrfmmm.2007.02.013" @default.
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