Lymphocyte DNA Damage and Anti-Oxidative Parameters are Affected by the Glutathione S-Transferase (GST) M1 and T1 Polymorphism and Smoking Status in Korean Young Adults

Jeong-Hwa Han; Hye-Jin Lee; Myung-Hee Kang

doi:10.4163/kjn.2011.44.5.366

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Han, Lee, and Kang: Lymphocyte DNA Damage and Anti-Oxidative Parameters are Affected by the Glutathione S-Transferase (GST) M1 and T1 Polymorphism and Smoking Status in Korean Young Adults

Research Article

Korean Journal of Nutrition

Korean Journal of Nutrition 2011; 44(5): 366-377.

Published online: 31 October 2011

DOI: https://doi.org/10.4163/kjn.2011.44.5.366

Lymphocyte DNA Damage and Anti-Oxidative Parameters are Affected by the Glutathione S-Transferase (GST) M1 and T1 Polymorphism and Smoking Status in Korean Young Adults

Jeong-Hwa Han, Hye-Jin Lee, Myung-Hee Kang

Department of Food & Nutrition, Daedeok Valley Campus, Hannam University, Daejeon 305-811, Korea.

To whom correspondence should be addressed. (mhkang@hnu.kr)

Received 29 September 2011 Revised 10 October 2011 Accepted 13 October 2011

Abstract

Glutathione S-transferase (GST) is a multigene family of phase II detoxifying enzymes that metabolize a wide range of exogenous and endogenous electrophilic compounds. GSTM1 and GSTT1 gene polymorphisms may account for inter-individual variability in coping with oxidative stress. We investigated the relationships between the level of lymphocyte DNA and antioxidative parameters and the effect on GST genotypes. GSTM1 and GSTT1 were characterized in 301 young healthy Korean adults and compared with oxidative stress parameters such as the level of lymphocyte DNA, plasma antioxidant vitamins, and erythrocyte antioxidant enzymes in smokers and non smokers. GST genotype, degree of DNA damage in lymphocytes, erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase (GSH-Px), and plasma concentrations of total radical-trapping antioxidant potential (TRAP), vitamin C, α- and γ-tocopherol, α- and β-carotene, and cryptoxanthin were analyzed. Lymphocyte DNA damage assessed by the comet assay was higher in smokers than that in non-smokers, but the levels of plasma vitamin C, β-carotene, TRAP, erythrocyte catalase, and GSH-Px were lower than those of non-smokers (p < 0.05). Lymphocyte DNA damage was higher in subjects with the GSTM1-null or GSTT1-present genotype than those with the GSTM1-present or GSTT1-null genotype. No difference in erythrocyte antioxidant enzyme activities, plasma TRAP, or vitamin levels was observed in subjects with the GSTM1 or GSTT1 genotypes, except β-carotene. Significant negative correlations were observed between lymphocyte DNA damage and plasma levels of TRAP and erythrocyte activities of catalase and GSH-Px after adjusting for smoking pack-years. Negative correlations were observed between plasma vitamin C and lymphocyte DNA damage only in individuals with the GSTM1-present or GSTT1-null genotype. The interesting finding was the significant positive correlations between lymphocyte DNA damage and plasma levels of α-carotene, β-carotene, and cryptoxanthin. In conclusion, the GSTM1-null and GSTT1-present genotypes as well as smoking aggravated antioxidant status through lymphocyte DNA damage. This finding confirms that GST polymorphisms could be important determinants of antioxidant status in young smoking and non-smoking adults. Consequently, the protective effect of supplemental antioxidants on DNA damage in individuals carrying the GSTM1-null or GSTT1-present genotypes might show significantly higher values than expected.

Keywords: oxidative stress, GST polymorphisms, antioxidative status, DNA damage, smokers

Figures and Tables

Fig. 1

Levels of lymphocyte DNA damage of smokers and nonsmokers, measured with the comet assay. Bars indicates S.E. of mean. ^*: p < 0.05, ^***: p < 0.001.

Fig. 2

Plasma concentration of vitamin C and β-carotene of smokers and non-smokers. Bars indicates S.E. of mean. ^**: p < 0.01, ^***: p < 0.001.

Fig. 3

Plasma levels of TRAP and erythrocyte catalase and glutathione peroxidase (GSH-Px) activities of smokers and non-smokers. Bars indicates S.E. of mean. ^***: p < 0.001.

Fig. 4

Lymphocyte tail length of the cell reflected DNA damage in the smokers and nonsmokers by GSTM1 or GSTT1 null/present genotype of the subjects. Bars indicates S.E. of mean. ^*: p < 0.05, ^**: p < 0.01, ^***: p < 0.001.

Fig. 5

Pearson's correlations between lymphocyte DNA damage (tail length) and their plasma antioxidant parameters or erythrocyte enzymes in the all subjects (n = 301) after adjusting smoking pack-years. r = Pearson's correlation coefficient, p = probability.

Table 1

Primer sequences used in the PCR reactions

Table 2

General characteristics of the subjects

1) All values are means ± S.E. 2) SBP: systolic blood pressure 3) DBP: diastolic blood pressure 4) Pack-years: (Cigarettes smoked/day × years smoked)/20

Table 3

Mean values of biomarkers in the subjects measured for GSTM1 gneotypes

1) Measured with the comet assay 2) Mean ± S.E. 3) Values of GSTM1-present genotype are significantly different from those of GSTM1-null genotype by Student t-test 4) NS: statistically not significant between GSTM1-present and GSTM1-null genotype by Student t-test

Table 4

Mean values of biomarkers in the subjects measured for GSTT1 gneotypes

Table 5

Effect of smoking and exercise on lymphocyte DNA damage according to the GSTM1 or GSTT1 genotypes in the subjects

1) Smoked 8 or more cigarettes/day for 6 months or longer 2) Mean ± S.E. 3) NS: Statistically not significant between GSTT1-present and GSTT1-null genotype by Student t-test 4) Currently not smoked 5) Values of GSTM1-present or GSTT1-present genotype are significantly different from those of GSTM1-null or GSTT1-null genotype by Student t-test 6) p-value of smoking effect by two-way ANOVA 7) p-value of GSTM1 or GSTT1 effect by two-way ANOVA

Table 6

Pearson's correlation coefficients between lymphocyte DNA damage and antioxidant-related parameters according to the GSTM1 and GSTT1 genotypes in the subjects after adjusting smoking pack-years

1) r = Pearson's correlation coefficients 2) p = probability 3) NS = not significant

Notes

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0069893).

References

1. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994. 50(4):1088–1101.

2. Cemeli E, Baumgartner A, Anderson D. Antioxidants and the Comet assay. Mutat Res. 2009. 681(1):51–67.

3. Porrini M, Riso P, Brusamolino A, Berti C, Guarnieri S, Visioli F. Daily intake of a formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection. Br J Nutr. 2005. 93(1):93–99.

4. Lagadu S, Lechevrel M, Sichel F, Breton J, Pottier D, Couderc R, Moussa F, Prevost V. 8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker of oxidative damage in oesophageal cancer patients: lack of association with antioxidant vitamins and polymorphism of hOGG1 and GST. J Exp Clin Cancer Res. 2010. 29:157.

5. Pool-Zobel BL, Bub A, Müller H, Wollowski I, Rechkemmer G. Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis. 1997. 18(9):1847–1850.

6. Noroozi M, Angerson WJ, Lean ME. Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. Am J Clin Nutr. 1998. 67(6):1210–1218.

7. Park YK, Park E, Kim JS, Kang MH. Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans. Mutat Res. 2003. 529(1-2):77–86.

8. Marcon F, Andreoli C, Rossi S, Verdina A, Galati R, Crebelli R. Assessment of individual sensitivity to ionizing radiation and DNA repair efficiency in a healthy population. Mutat Res. 2003. 541(1-2):1–8.

9. Sinha R, Caporaso N. Diet, genetic susceptibility and human cancer etiology. J Nutr. 1999. 129:2S Suppl. 556S–559S.

10. Hoffmann H, Isner C, Högel J, Speit G. Genetic polymorphisms and the effect of cigarette smoking in the comet assay. Mutagenesis. 2005. 20(5):359–364.

11. Strange RC, Fryer AA. The glutathione S-transferases: influence of polymorphism on cancer susceptibility. IARC Sci Publ. 1999. (148):231–249.

12. Awasthi YC, Sharma R, Singhal SS. Human glutathione S-transferases. Int J Biochem. 1994. 26(3):295–308.

13. Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev. 1997. 6(9):733–743.

14. Nan HM, Kim H, Lim HS, Choi JK, Kawamoto T, Kang JW, Lee CH, Kim YD, Kwon EH. Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1, GSTM1 and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentrations. Carcinogenesis. 2001. 22(5):787–793.

15. Ye Z, Song H. Glutathione s-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta-analysis. Eur J Cancer. 2005. 41(7):980–989.

16. Davies SM, Bhatia S, Ross JA, Kiffmeyer WR, Gaynon PS, Radloff GA, Robison LL, Perentesis JP. Glutathione S-transferase genotypes, genetic susceptibility, and outcome of therapy in childhood acute lymphoblastic leukemia. Blood. 2002. 100(1):67–71.

17. Masetti S, Botto N, Manfredi S, Colombo MG, Rizza A, Vassalle C, Clerico A, Biagini A, Andreassi MG. Interactive effect of the glutathione S-transferase genes and cigarette smoking on occurrence and severity of coronary artery risk. J Mol Med (Berl). 2003. 81(8):488–494.

18. Palma S, Cornetta T, Padua L, Cozzi R, Appolloni M, Ievoli E, Testa A. Influence of glutathione S-transferase polymorphisms on genotoxic effects induced by tobacco smoke. Mutat Res. 2007. 633(1):1–12.

19. Park E, Kang MH. Smoking and high plasma triglyceride levels as risk factors for oxidative DNA damage in the Korean population. Ann Nutr Metab. 2004. 48(1):36–42.

20. Jeon GI, Park E. Effect of glutathione S-transferase polymorphisms on the antioxidant system. J Korean Soc Food Sci Nutr. 2007. 36(6):708–719.

21. Jo HR, Lee HJ, Kang MH. Antioxidative status, DNA damage and lipid profiles in Korean young adults by glutathione S-transferase polymorphisms. Korean J Nutr. 2011. 44(1):16–28.

22. Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J. 1994. 300(Pt 1):271–276.

23. Bell DA, Taylor JA, Paulson DF, Robertson CN, Mohler JL, Lucier GW. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst. 1993. 85(14):1159–1164.

24. Park EJ, Kim JS, Jeon EJ, Kim HY, Park YK, Kang MH. The effects of purple grape juice supplementation on improvement of antioxidant status and lymphocyte DNA damage in Korean smokers. Korean J Nutr. 2004. 37(4):281–290.

25. Kim YD, Eom SY, Zhang YW, Kim H, Park JD, Yu SD, Lee CH, Arashidani K, Kawamoto T, Kim H. Modification of the relationship between urinary 8-OHdG and hippuric acid concentration by GSTM1, GSTT1, and ALDH2 genotypes. Hum Exp Toxicol. 2011. 30(4):338–342.

26. McGill HC Jr. The cardiovascular pathology of smoking. Am Heart J. 1988. 115(1 Pt 2):250–257.

27. Topinka J, Binková B, Mracková G, Stávková Z, Peterka V, Benes I, Dejmek J, Lenícek J, Pilcík T, Srám RJ. Influence of GSTM1 and NAT2 genotypes on placental DNA adducts in an environmentally exposed population. Environ Mol Mutagen. 1997. 30(2):184–195.

28. Bennett WP, Alavanja MC, Blomeke B, Vähäkangas KH, Castrén K, Welsh JA, Bowman ED, Khan MA, Flieder DB, Harris CC. Environmental tobacco smoke, genetic susceptibility and risk of lung cancer in never-smoking women. J Natl Cancer Inst. 1999. 91(23):2009–2014.

29. Dusinská M, Ficek A, Horská A, Raslová K, Petrovská H, Vallová B, Drlicková M, Wood SG, Stupáková A, Gasparovic J, Bobek P, Nagyová A, Kováciková Z, Blazícek P, Liegebel U, Collins AR. Glutathione S-transferase polymorphisms influence the level of oxidative DNA damage and antioxidant protection in humans. Mutat Res. 2001. 482(1-2):47–55.

30. Reszka E, Wasowicz W, Gromadzinska J. Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility. Br J Nutr. 2006. 96(4):609–619.

31. Palli D, Masala G, Vineis P, Garte S, Saieva C, Krogh V, Panico S, Tumino R, Munnia A, Riboli E, Peluso M. Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults. Carcinogenesis. 2003. 24(4):739–746.

32. Wang Y, Ichiba M, Oishi H, Iyadomi M, Shono N, Tomokuni K. Relationship between plasma concentrations of beta-carotene and alpha-tocopherol and life-style factors and levels of DNA adducts in lymphocytes. Nutr Cancer. 1997. 27(1):69–73.

33. Wang Y, Ichiba M, Iyadomi M, Zhang J, Tomokuni K. Effects of genetic polymorphism of metabolic enzymes, nutrition, and lifestyle factors on DNA adduct formation in lymphocytes. Ind Health. 1998. 36(4):337–346.

34. Brennan P, Hsu CC, Moullan N, Szeszenia-Dabrowska N, Lissowska J, Zaridze D, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Gemignani F, Chabrier A, Hall J, Hung RJ, Boffetta P, Canzian F. Effect of cruciferous vegetables on lung cancer in patients stratified by genetic status: a mendelian randomisation approach. Lancet. 2005. 366(9496):1558–1560.

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