Modification of urinary N7-methylguanine excretion in smokers by glutathione-S-transferase M1 polymorphism.
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+/-305 ng/mg creatinine [standard error] vs. 2386+/-153 ng/mg creatinine; P=0.01). Higher N7-MeG concentrations were observed with the GSTM1 null genotype than with the GSTM1 non-null genotype (3230+/-292 ng/mg creatinine vs. 2336+/-153 ng/mg creatinine; P=0.007), particularly in smokers (3775+/-483 ng/mg creatinine vs. 2468+/-228 ng/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.
Lin
I-Hsin
IH
Department of Public Health, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan.
Chao
Mu-Rong
MR
Hu
Chiung-Wen
CW
Ho
Ming-Lin
ML
Huang
Jo-Yun
JY
Lee
Hong-Shen
HS
Chen
Chun-Chieh
CC
Wong
Ruey-Hong
RH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012907:Smoking / Q000235:genetics / Q000652:urine*; D055815:Young Adult
D004247:DNA; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006147:Guanine; C008450:7-methylguanine; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human