Abstract
ObjectiveCigarette smoking is a major risk factor for atherosclerotic cardiovascular disease, which is responsible for a significant proportion of smoking-related deaths. However, the precise mechanism whereby smoking induces this pathology has not been fully delineated. Based on observation of DNA double-strand breaks (DSBs), the most harmful type of DNA damage, in atherosclerotic lesions, we hypothesized that there is a direct association between smoking and DSBs. The goal of this study was to investigate whether smoking induces DSBs and smoking cessation reverses DSBs in vivo through examination of peripheral mononuclear cells (MNCs).Approach and ResultsImmunoreactivity of oxidative modification of DNA and DSBs were increased in human atherosclerotic lesions but not in the adjacent normal area. DSBs in human MNCs isolated from the blood of volunteers can be detected as cytologically visible “foci” using an antibody against the phosphorylated form of the histone H2AX (γ-H2AX). Young healthy active smokers (n = 15) showed increased γ-H2AX foci number when compared with non-smokers (n = 12) (foci number/cell: median, 0.37/cell; interquartile range [IQR], 0.31–0.58 vs. 4.36/cell; IQR, 3.09–7.39, p<0.0001). Smoking cessation for 1 month reduced the γ-H2AX foci number (median, 4.44/cell; IQR, 4.36–5.24 to 0.28/cell; IQR, 0.12–0.53, p<0.05). A positive correlation was noted between γ-H2AX foci number and exhaled carbon monoxide levels (r = 0.75, p<0.01).ConclusionsSmoking induces DSBs in human MNCs in vivo, and importantly, smoking cessation for 1 month resulted in a decrease in DSBs to a level comparable to that seen in non-smokers. These data reinforce the notion that the cigarette smoking induces DSBs and highlight the importance of smoking cessation.
Highlights
Cigarette smoking is a major risk factor for atherosclerotic cardiovascular disease
Smoking induces double-strand breaks (DSBs) in human mononuclear cells (MNCs) in vivo, and importantly, smoking cessation for 1 month resulted in a decrease in DSBs to a level comparable to that seen in non-smokers
DSBs are present in human atherosclerotic plaques To investigate whether DNA damage and repair is involved in the pathogenesis of atherosclerosis, atherosclerotic lesions obtained from autopsy were evaluated by immunohistochemistry
Summary
Cigarette smoking is a major risk factor for atherosclerotic cardiovascular disease. The molecular mechanisms by which smoking promotes atherosclerosis have not been fully delineated. Cigarette smoke contains thousands of chemicals and compounds, including many oxidants and free radicals that induce oxidative damage. Cigarette smoke causes oxidative damage in DNA, either directly or through generation of reactive oxygen species in cultured cells [3]. While most DNA damage caused by reactive oxygen species, chemicals, radiation, and other noxious stimuli is efficiently repaired by specific DNA repair systems, persistence and accumulation of DNA damage can occur depending on the severity of the damage and the capacity of DNA repair mechanisms. Accumulated DNA damage results in mutagenesis and chromosomal rearrangements, leading to genomic instability
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
