Alkylation and oxidative‐DNA damage repair activity in blood leukocytes of smokers and non‐smokers

Abstract

The levels of 3 DNA repair enzymes involved in alkylation and oxidative DNA damage repair in human peripheral blood leukocytes were measured in 20 smokers and 17 non-smokers. No differences in O6-alkylguanine-DNA-alkyltransferase (AGT) activity were found between the 2 groups and the AGT distribution within the population appeared to be unimodal. In contrast, the mean activities of both the methylpurine (MeP)- and the 2-6-diamino-4-hydroxy-5N formamidopyrimidine (FaPy)-DNA glycosylases were higher in the smokers, although only the difference between the MeP-DNA glycosylase means was statistically significant. The standard deviations of these 2 enzymes were also higher in the smokers. The MeP-DNA glycosylase activity showed a bimodal distribution when all subjects were considered. This may in part be due to the smoking habit; 83% of the subjects with enzyme activities higher than 500 fmoles/mg protein were current smokers, whilst 85% of the non-smokers had lower enzyme activities. However, if the smokers were considered separately, a bimodal distribution of this enzyme activity could still be observed. No strong correlation was observed between enzyme activity and age, although the slopes of the regression lines of enzyme activity on age were all negative. The relationship between enzyme activities was studied by bivariate distribution and a strong correlation was only found between the MeP-DNA glycosylase and the FaPy-glycosylase, with the highest values of both enzyme activities being observed in the smokers and the lowest in the non-smokers. Our results suggest that the activity of certain DNA repair enzymes can be modulated by environmental exposure.

Autophagy-Dependent Regulation of the DNA Damage Response Protein Ribonucleotide Reductase 1

“…Transcriptional profiling studies of S. cerevisiae have demonstrated that alkylation damage induces the transcription of hundreds of genes corresponding to proteins associated with DNA repair, cell-cycle checkpoints, amino acid metabolism and protein degradation (7)(8)(9)(10)(11). Protein degradation has been observed previously for components of the DNA damage response (12,13) and, in theory, can work to optimize essential enzyme activity. In addition, protein degradation is used to remove damaged or unfolded proteins.…”

Tetracycline‐dependent regulation offormamidopyrimidine DNA glycosylasein transgenic mice conditionally reduces oxidative DNA damagein vivo

“…In humans, enzymatic activities for the repair of oxidized DNA can vary up to 100‐fold (45), and the levels of 8‐oxo‐dG in lymphocytes vary sixfold in the population (46), suggesting that there may be subsets of the population that are at risk for increased levels of 8‐oxo‐dG. We have demonstrated herein that it is possible to regulate the endogenous level of 8‐oxo‐dG in vivo , in binary transgenic actin‐tTA:tetO‐fpg mice overexpressing the bacterial fpg DNA repair enzyme.…”

Oxidative DNA Damage and Human Cancer: Need for Cohort Studies

“…A number of studies have found the expected higher levels of 8-oxodG and other oxidative bases or strand breaks in leukocyte DNA from smokers as compared with nonsmokers, although this is far from consistent (10,28,47,52). Inconsistencies may be due to possible induction of OGG1 activity by smoking (28,34). Exposure to ambient air particles and benzene has consistently been associated with high levels of 8-oxodG in lymphocytes (2,81,82,92).…”

“…The capacity for nicking of labeled oligonucleotides with, for example, oxidized bases or ethenoadducts by extracts of cells or tissues is measured relatively easily (34,84). Similarly, cell extracts can be applied on nucleoids with a defined level of, for example, 8-oxodG induced by a photosensitizer and nicking assessed by the comet assay (16).…”