Korean J Nutr.  2011 Oct;44(5):366-377. 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

• Han JH
• Lee HJ
• Kang MH

• KMID: 2268560
• DOI: http://doi.org/10.4163/kjn.2011.44.5.366

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, alpha- and gamma-tocopherol, alpha- and beta-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, beta-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 beta-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 alpha-carotene, beta-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.

Keyword

oxidative stress; GST polymorphisms; antioxidative status; DNA damage; smokers

MeSH Terms

Adult
Antioxidants
Ascorbic Acid
beta Carotene
Carotenoids
Catalase
Comet Assay
DNA
DNA Damage
Erythrocytes
gamma-Tocopherol
Genotype
Glutathione
Glutathione Peroxidase
Glutathione Transferase
Humans
Lifting
Lymphocytes
Multigene Family
Oxidative Stress
Plasma
Smoke
Smoking
Superoxide Dismutase
Vitamins
Xanthophylls
Young Adult
Antioxidants
Ascorbic Acid
Carotenoids
Catalase
DNA
Glutathione
Glutathione Peroxidase
Glutathione Transferase
Smoke
Superoxide Dismutase
Vitamins
Xanthophylls
beta Carotene
gamma-Tocopherol

Figure

• 

  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.

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