Modification of the relationship between urinary 8-OHdG and hippuric acid concentration by GSTM1,GSTT1,and ALDH2 genotypes

Abstract

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hippuric acid (HA) has been widely used as a biological marker of occupational exposure to toluene, although it is no longer valid for low levels of toluene exposure.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.

Keywords

hippuric acid oxidative DNA damage genetic polymorphism GSTM1 GSTT1 ALDH2

References

Pierce CH , Chen Y. , Dills RL , Kalman DA , Morgan MS Toluene metabolites as biological indicators of exposure. Toxicol Lett 2002; 129: 65-76.

Mattia CJ , Ali SF , Bondy SC Toluene-induced oxidative stress in several brain regions and other organs . Mol Chem Neuropathol 1993; 18: 313-328.

Murata M. , Tsujikawa M. , Kawanishi S. Oxidative DNA damage by minor metabolites of toluene may lead to carcinogenesis and reproductive dysfunction. Biochem Biophys Res Commun 1999; 261: 478-483.

Kawai T. , Ukai H. , Inoue O. , Maejima Y. , Fukui Y. , Ohashi F. , Okamoto S. , et al. Evaluation of biomarkers of occupational exposure to toluene at low levels. Int Arch Occup Environ Health 2008; 81: 253-262.

Ukai H. , Kawai T. , Inoue O. , Maejima Y. , Fukui Y. , Ohashi F. , et al. Comparative evaluation of biomarkers of occupational exposure to toluene. Int Arch Occup Environ Health 2007; 81: 81-93.

Nan HM , Kim H. , Lim HS , Choi JK , Kawamoto T. , Kang JW , et al. Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1, GSTM1 and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentrations. Carcinogenesis 2001; 22: 787-793.

Laham S. , Potvin M. Biological conversion of benzaldehyde to benzylmercapturic acid in the Sprague-Dawley rat. Drug Chem Toxicol 1987; 10: 209-225.

Waniusiow D. , Campo P. , Venet T. , Cossec B. , Cosnier F. , Beydon D. , et al. Toluene-induced hearing loss in the guinea pig. Toxicol Sci 2009; 111: 362-371.

Chen C. , Madeleine MM , Lubinski C. , Weiss NS , Tickman EW , Daling JR Glutathione S-transferase M1 genotypes and the risk of anal cancer: a population-based case-control study. Cancer Epidemiol Biomarkers Prev 1996; 5: 985-991.

10.

Munaka M. , Katoh T. , Kohshi K. , Sasaki S. Influence of tea and coffee on biomonitoring of toluene exposure. Occup Med (Lond) 2009; 59: 397-401.

11.

Kawamoto T. , Matsuno K. , Kodama Y. , Murata K. , Matsuda S. ALDH2 polymorphism and biological monitoring of toluene. Arch Environ Health 1994; 49: 332-336.

12.

Kawamoto T. , Koga M. , Murata K. , Matsuda S. , Kodama Y. Effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on toluene metabolism in humans . Toxicol Appl Pharmacol 1995; 133: 295-304.

13.

Lo HW , Ali-Osman F. Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Curr Opin Pharmacol 1995; 7: 367-374.

14.

Breton CV , Kile ML , Catalano PJ , Hoffman E. , Quamruzzaman Q. , Rahman M. , et al. GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated measures study. Environ Health 2007; 6: 39.

15.

Lin YS , Hung SC , Wei YH , Tarng DC GSTM1 polymorphism associates with DNA oxidative damage and mortality among hemodialysis patients. J Am Soc Nephrol 2009 ; 20: 405-415.

16.

Chen SS , Chang LS , Chen HW , Wei YH Polymorphisms of glutathione S-transferase M1 and male infertility in Taiwanese patients with varicocele. Hum Reprod 2002; 17: 718-725.

17.

Inoue O. , Seiji K. , Watanabe T. , Nakatsuka H. , Jin C. , Liu SJ , et al. Effects of smoking and drinking on excretion of hippuric acid among toluene-exposed workers. Int Arch Occup Environ Health 1993; 64: 425-430.