Modification of urinary N7-methylguanine excretion in smokers by glutathione- S -transferase M1 polymorphism

• Published in: Toxicology (Amsterdam) Vol. 260; no. 1; pp. 1 - 6
• Main Authors: Lin, I-Hsin, Chao, Mu-Rong, Hu, Chiung-Wen, Ho, Ming-Lin, Huang, Jo-Yun, Lee, Hong-Shen, Chen, Chun-Chieh, Wong, Ruey-Hong
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 16.06.2009; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cross-Sectional Studies; DNA - chemistry; DNA - genetics; Emergency; Female; Genotype; Glutathione S-Transferase pi - genetics; Glutathione S-Transferase pi - metabolism; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; GSTM1 gene; Guanine - analogs & derivatives; Guanine - urine; Humans; Male; Medical sciences; Middle Aged; N7-Methylguanine; Polymerase Chain Reaction; Polymorphism, Genetic; Smoking; Smoking - genetics; Smoking - urine; Tobacco, tobacco smoking; Toxicology; Young Adult; N7-Methylguanine; GSTM1 gene; Smoking; Human; Urine; Modification; Excretion; Genetic variability; Enzyme; Isozyme; Transferases; Tobacco smoking; Genotype; Gene; Smoker; Glutathione transferase; Genetics; Polymorphism
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2009.02.015

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 ± 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.