Modification of the relationship between urinary 8-OHdG and hippuric acid concentration by GSTM1, GSTT1, and ALDH2 genotypes.
Urinary hippuric acid (HA) has been widely used as a biological marker of occupational exposure to toluene, although it is no longer valid for low levels of toluene exposure. Toluene exposure is known to induce oxidative DNA damage and the metabolism is affected by genetic polymorphisms of some metabolizing enzymes. Therefore, genetic polymorphisms of these metabolizing enzymes must be considered in the evaluation of oxidative stress caused by toluene exposure. We evaluated the relationship between urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and urinary HA in individuals without occupational exposure to toluene and characterized the possible roles of GSTM1, GSTT1, and aldehyde dehydrogenase 2 (ALDH2) genotypes in the relationships between these markers. In this study, we enrolled 92 healthy Koreans. Urinary HA and 8-OHdG levels were measured and the correlations between them were statistically tested according to the GSTM1, GSTT1, and ALDH2 genotypes. HA did not significantly correlate with urinary 8-OHdG in overall subjects. However, the correlation between them showed a statistical significance in individuals with GSTM1-null, GSTT1-null, and ALDH2 *2/*2 genotypes (r = 0.766, p < 0.01). This study shows that the relationship between urinary HA and 8-OHdG concentration is modified by genetic polymorphisms of some metabolizing enzymes such as GSTM1, GSTT1, and ALDH2.
Kim
Yong-Dae
YD
Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
Eom
Sang-Yong
SY
Zhang
Yan Wei
YW
Kim
Hyeongsu
H
Park
Jung-Duk
JD
Yu
Seung-Do
SD
Lee
Chul-Ho
CH
Arashidani
Keiichi
K
Kawamoto
Toshihiro
T
Kim
Heon
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006626:Hippurates / Q000652:urine*; D006801:Humans; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects; D011110:Polymorphism, Genetic; D014050:Toluene / Q000009:adverse effects
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D015415:Biomarkers; D003849:Deoxyguanosine; D005982:Glutathione Transferase; D006626:Hippurates; D014050:Toluene; C096127:ALDH2 protein, human; C413545:glutathione S-transferase T1; C030514:hippuric acid