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Reduction in oxidatively generated DNA damage following smoking cessation.

Box HC, O'Connor RJ, Patrzyc HB, Iijima H, Dawidzik JB, Freund HG, Budzinski EE, Cummings KM, Mahoney MC - Tob Induc Dis (2011)

Bottom Line: The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.The d(TgpA) and d(PfpA) lesions show relatively greater rebound at Week 16 compared to the d(Gh) lesion (88% of baseline for d(TgpA), 64% of baseline for d(PfpA), vs 46% of baseline for d(Gh)).Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. richard.oconnor@roswellpark.org.

ABSTRACT

Background: Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.

Methods: Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(TgpA)]; formamide breakdown of pyrimidine bases [d(TgpA)]; 8-oxo-7,8-dihydroguanine [d(Gh)]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition.

Results: Overall time effects for the d(TgpA) (χ2(3) = 8.068, p < 0.045), d(PfpA) (χ2(3) = 8.477, p < 0.037), and d(Gh) (χ2(3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(TgpA) and d(PfpA) lesions show relatively greater rebound at Week 16 compared to the d(Gh) lesion (88% of baseline for d(TgpA), 64% of baseline for d(PfpA), vs 46% of baseline for d(Gh)).

Conclusions: Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.

No MeSH data available.


Related in: MedlinePlus

Individual patterns of change in lesion levels by study week.
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Figure 3: Individual patterns of change in lesion levels by study week.

Mentions: The results of measurements of d(TgpA), d(PfpA), and d(Gh) modifications are presented in Table 2 for each of the four time points. The mean values of the measurements and SEM's are given in terms of femtomoles (fmol) of lesions per microgram (μg) of DNA. Figure 3 illustrates the interindividual variability in measurements at each timepoint as well as changes across time. An overall pattern was apparent for all 3 markers demonstrating decreases over time coinciding with stopping smoking. Two biomarkers (d(TgpA) and d(PfpA)) increased on average at the final measurement. Results of generalized estimating equation analysis (accounting for gender, age, and treatment condition; see Table 3) showed significant overall time effects for the d(TgpA) (χ2(3) = 9.389, p < 0.025), d(PfpA) (χ2(3) = 9.070, p < 0.028), and d(Gh) (χ2(3) = 37.236, p < 0.001) lesions, indicating levels of each decreased significantly after smoking cessation. The d(TgpA) and d(PfpA) lesions show relatively greater rebound at TQD+11 weeks compared to the d(Gh) lesion (88% of baseline for d(TgpA), 64% of baseline for d(PfpA), vs 46% of baseline for d(Gh). Indeed, the GEE models show that the value 11 weeks following TQD is not statistically different from the baseline value for d(TgpA), however those differences are significant for d(PfpA) and d(Gh). We did not see a significant association of lesion levels with age or gender. In the case of the d(Gh) lesion, we observed a statistically significant treatment group difference (χ2(1) = 4.910, p < 0.027), wherein those in the treatment arm had overall significantly higher d(Gh) levels (23.0 versus 18.1).


Reduction in oxidatively generated DNA damage following smoking cessation.

Box HC, O'Connor RJ, Patrzyc HB, Iijima H, Dawidzik JB, Freund HG, Budzinski EE, Cummings KM, Mahoney MC - Tob Induc Dis (2011)

Individual patterns of change in lesion levels by study week.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104490&req=5

Figure 3: Individual patterns of change in lesion levels by study week.
Mentions: The results of measurements of d(TgpA), d(PfpA), and d(Gh) modifications are presented in Table 2 for each of the four time points. The mean values of the measurements and SEM's are given in terms of femtomoles (fmol) of lesions per microgram (μg) of DNA. Figure 3 illustrates the interindividual variability in measurements at each timepoint as well as changes across time. An overall pattern was apparent for all 3 markers demonstrating decreases over time coinciding with stopping smoking. Two biomarkers (d(TgpA) and d(PfpA)) increased on average at the final measurement. Results of generalized estimating equation analysis (accounting for gender, age, and treatment condition; see Table 3) showed significant overall time effects for the d(TgpA) (χ2(3) = 9.389, p < 0.025), d(PfpA) (χ2(3) = 9.070, p < 0.028), and d(Gh) (χ2(3) = 37.236, p < 0.001) lesions, indicating levels of each decreased significantly after smoking cessation. The d(TgpA) and d(PfpA) lesions show relatively greater rebound at TQD+11 weeks compared to the d(Gh) lesion (88% of baseline for d(TgpA), 64% of baseline for d(PfpA), vs 46% of baseline for d(Gh). Indeed, the GEE models show that the value 11 weeks following TQD is not statistically different from the baseline value for d(TgpA), however those differences are significant for d(PfpA) and d(Gh). We did not see a significant association of lesion levels with age or gender. In the case of the d(Gh) lesion, we observed a statistically significant treatment group difference (χ2(1) = 4.910, p < 0.027), wherein those in the treatment arm had overall significantly higher d(Gh) levels (23.0 versus 18.1).

Bottom Line: The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.The d(TgpA) and d(PfpA) lesions show relatively greater rebound at Week 16 compared to the d(Gh) lesion (88% of baseline for d(TgpA), 64% of baseline for d(PfpA), vs 46% of baseline for d(Gh)).Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. richard.oconnor@roswellpark.org.

ABSTRACT

Background: Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.

Methods: Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(TgpA)]; formamide breakdown of pyrimidine bases [d(TgpA)]; 8-oxo-7,8-dihydroguanine [d(Gh)]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition.

Results: Overall time effects for the d(TgpA) (χ2(3) = 8.068, p < 0.045), d(PfpA) (χ2(3) = 8.477, p < 0.037), and d(Gh) (χ2(3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(TgpA) and d(PfpA) lesions show relatively greater rebound at Week 16 compared to the d(Gh) lesion (88% of baseline for d(TgpA), 64% of baseline for d(PfpA), vs 46% of baseline for d(Gh)).

Conclusions: Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.

No MeSH data available.


Related in: MedlinePlus