1. Modification of urinary N7-methylguanine excretion in smokers by glutathione-S-transferase M1 polymorphism
- Author
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Lin, I-Hsin, Chao, Mu-Rong, Hu, Chiung-Wen, Ho, Ming-Lin, Huang, Jo-Yun, Lee, Hong-Shen, Chen, Chun-Chieh, and Wong, Ruey-Hong
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PHYSIOLOGICAL effects of tobacco , *GLUTATHIONE transferase , *GENETIC polymorphisms , *DNA adducts , *METHYLATION , *TOBACCO smoke , *URINALYSIS , *CARCINOGENS , *CREATININE , *TANDEM mass spectrometry - Abstract
Abstract: Tobacco smoke contains many carcinogens which can lead to DNA methylation. Glutathione-S-transferases (GSTs) are detoxifying enzymes, and the effects of the genes GSTM1, GSTT1, and GSTP1 on cigarette smoke-induced methylated adducts have not been elucidated. Therefore, we investigated the association of the GSTM1, GSTT1, and GSTP1 genes and N7-methylguanine (N7-MeG) adducts in smokers. Urinary N7-MeG concentrations were measured by using liquid chromatography–tandem mass spectrometry in 112 smokers and 89 non-smokers, and GSTM1, GSTT1, and GSTP1 genotypes were identified by polymerase chain reaction. Smokers had higher N7-MeG concentrations than did non-smokers (3238±305ng/mg creatinine [standard error] vs. 2386±153ng/mg creatinine; P =0.01). Higher N7-MeG concentrations were observed with the GSTM1 null genotype than with the GSTM1 non-null genotype (3230±292ng/mg creatinine vs. 2336±153ng/mg creatinine; P =0.007), particularly in smokers (3775±483ng/mg creatinine vs. 2468±228ng/mg creatinine; P =0.02). However, the GSTT1 and GSTP1 genotypes were not associated with urinary N7-MeG concentrations. Therefore, the susceptible GSTM1 genotype may modulate the concentrations of N7-MeG adducts in the DNA of smokers. [Copyright &y& Elsevier]
- Published
- 2009
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