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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

DNA dimer modifications under investigation.
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Figure 1: DNA dimer modifications under investigation.

Mentions: An issue with the existing literature is the reliance on the d(Gh) lesion as the primary indicator of oxidatively-induced DNA damage from cigarette smoking. This base modification is not a significant product of deoxyguanosine exposed in vitro to hydroxyl radicals [19]. In addition, the facile oxidation of guanine leads to artifactual production of d(Gh). A preferable approach may be to examine base modifications that unequivocally can be associated with hydroxyl radical activity. Modern mass spectrometry now makes it feasible to measure the levels of multiple oxidatively-induced DNA lesions simultaneously. Two such alternative base modifications are a) the glycol modification of thymine [d(TgpA)], and b) the formamide breakdown product of pyrimidine bases [d(PfpA)]. The structures of these modifications are shown in Figure 1 in the form they are measured. Included in Figure 1 is the structure of d(Gh), the DNA modification most often used as an indicator of oxidative stress.


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)

DNA dimer modifications under investigation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: DNA dimer modifications under investigation.
Mentions: An issue with the existing literature is the reliance on the d(Gh) lesion as the primary indicator of oxidatively-induced DNA damage from cigarette smoking. This base modification is not a significant product of deoxyguanosine exposed in vitro to hydroxyl radicals [19]. In addition, the facile oxidation of guanine leads to artifactual production of d(Gh). A preferable approach may be to examine base modifications that unequivocally can be associated with hydroxyl radical activity. Modern mass spectrometry now makes it feasible to measure the levels of multiple oxidatively-induced DNA lesions simultaneously. Two such alternative base modifications are a) the glycol modification of thymine [d(TgpA)], and b) the formamide breakdown product of pyrimidine bases [d(PfpA)]. The structures of these modifications are shown in Figure 1 in the form they are measured. Included in Figure 1 is the structure of d(Gh), the DNA modification most often used as an indicator of oxidative stress.

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