Open Access
Subscription Access
Open Access
Subscription Access
Role of Glutathione-S-Transferase Polymorphism on Arsenic Induced DNA Hypermethylation
Subscribe/Renew Journal
People chronically exposed to environmental arsenic through their drinking water experience various arsenic induced clinical manifestations and there is modulation of methylation level in their genome. However the response varies widely among persons. The present manuscript deals with the evaluation of role of individual's GST status in altering the degree of DNA methylation after chronic arsenic exposure in human. To study whether Glutathione-S-Transferase (GST) gene polymorphism plays any role in this variation, a total of 92 study subjects were recruited from the villages of southern region of West Bengal, India. Concentration of arsenic in their urine and water, extent of clinical manifestation, GST status and p53 and p16 gene promoter methylation status were determined. Results showed that genetic polymorphism of GSTM1 and T1 were significantly associated (p<0.05) with degree of methylation in p53 and p16 gene promoter region and urinary arsenic in higher exposure group. Persons having null genotype have significantly decreased urinary arsenic and increased DNA methylation level relative to persons with GSTM1 or GSTT1 nonnull genotype of same arsenic exposure group. In the present work we are therefore trying to show that individual's GST polymorphic status may alter the degree of DNA methylation after arsenic exposure.
Keywords
Arsenic, Clinical Symptom Score, DNA Hypermethylation, GST Polymorphism, Total Urinary Arsenic.
User
Subscription
Login to verify subscription
Font Size
Information
- Aposhian HV. Enzymatic methylation of arsenic species and other new approaches to arsenic. Ann Rev of Pharm and Tox. 1997; 37:397–419.
- Thompson DJ. A chemical hypothesis for arsenic methylation in mammals. Chemico-Biologic Inter.1993; 88:89–114.
- Vahter M. Variation in human metabolism of arsenic. Arsenic Exposure and Health Effects. 2nd ed. 1999; 267–75.
- Mass MJ, Wang L. Arsenic alters cytocine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: A model for a mechanism of carcinogenecis. Mutat Res. 1997; 386:263–77.
- Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP. Association of arsenic- induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci. 1997; 94:10907–12.
- Zhong CX, Mass MJ. Both hypomethylation and hypermethylation of DNA associated with arsenite exposure in cultures of human cells identified by methylation-sensitive arbitrarily-primed PCR. Toxicol Lett. 2001; 122:223–34.
- Liu J, Xie Y, Ward JM, Diwan BA, Waalkes MP. Toxicogenomics analysis of aberrant gene expression in liver tumors and nontumorous livers of adult mice exposed in utero to inorganic arsenic. Toxicol Sci. 2004; 77:249–57.
- Chanda S, Dasgupta UB, Mazumder DG, Gupta M, Chaudhuri U, Lahiri S, et al. DNA Hypermethylation of Promoter of Gene p53 and p16 in arsenic-exposed People with and without Malignancy. Toxicol Sci. 2006; 89:431–7.
- Atallah R, Kalman DA. Online photooxidation for the determination of organic arsenic compounds by AAS with continuous arsine generation. Talanta. 1991; 38:167–73.
- Mondal BC, Paria N, Majumder S, Chandra S, Mukhopadhyay A, Chaudhuri U, et al. Glutathione-S-transferase M1 and T1 null genotype frequency in chronic myeloid leukemia. Europian Journal of Cancer Prevention. 2005; 14:281–4.
- Allen T, Rana SV. Effect of arsenic (AsIII) on glutathionedependent enzymes in liver and kidney of the freshwater fish Channa punctatus . Biol Trace Elem Res. 2004; 100:39–48.
- Ntebogeng S, Flores-Tavizón E, Castillo-Michel H, PeraltaVidea JR, Gardea-Torresdey JL. Arsenic tolerance in mesquite (Prosopis sp.): Low molecular weight thiols synthesis and glutathione activity in response to arsenic. Plant Physiol and Biochem. 2009; 47:822–6.
- Engstrom KS, Broberg K, Concha G, Nermell B, Warholm M, Vahter M. Genetic polymorphisms influencing arsenic metabolism: Evidence from argentina. Environ Health Perspect. 2007; 115:599–605.
- Engstrom KS, Vahter M, Mlakar SJ, Concha G, Nermell B, Raqib R, et al. Polymorphisms in arsenic(+III oxidation state) methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism. Environ Health Perspec. 2011; 119:182–8.
- Steinmaus C, Moore LE, Shipp M, Kalman D, Rey OA, Biggs ML, et al. Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic. J Tox Environ Health, Part A. 2007; 70:159–70.
- Agusa T, Iwata H, Fujihara J, Kunito T, Takeshita H, Minh TB, et al. Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta Vietnam. Toxicol Appl Pharmacol. 2010; 242:352–62.
- Lin GF, Du H, Chen JG, Lu HC, Kai JX, Zhou YS, et al. Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China. Arch Toxicol. 2007; 81:545–51.
- McCarty KM, Chen YC, Quamruzzaman Q, Rahman M, Mahiuddin G, Hsueh YM, et al. Arsenic Methylation, GSTT1, GSTM1, GSTP1 Polymorphisms, and Skin Lesions. Environ Health Perspect. 2007; 115:341–5.
- Marcos R, Martínez V, Hernández A, Creus A, Sekaran C, Tokunaga H, et al. Metabolic profile in workers occupationally exposed to arsenic: Role of GST polymorphisms. J Occup Environ Med. 2006; 48:334–41.
- Chiou HY, Hsueh YM, Hsieh LL, Hsu LI, Hsu YH, Hsieh FI, et al. Arsenic methylation capacity, body retention and null genotypes of glutathione S-transferase M1 and T1 among current arsenic –exposed residents in Taiwan. Mut Res. 1997; 386:197–207.
- Kile ML, Houseman AE, Rodrigues ETJ, Quamruzzaman Q, Rahman M, Mahiuddin G, et al. Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking water. Cancer Epidemiol Biomarkers Prev. 2005; 14:2419–26.
- Dumond JW, Sing KP. Gene expression changes and induction of cell proliferation by chronic exposure to arsenic of mouse testicular leydig cells. J Tox and Environ Health A. 2007; 70:1150–4.
- Majumder S, Chanda S, Ganguli B, Mazumder DN, Lahiri S, Dasgupta UB, et al. Arsenicexposure induces genomic hypermethylation. Environ Toxicol. 2010; 25(3):315–8.
- Chanda S, Dasgupta UB, Mazumder DNG, Saha J, Gupta B. Human GMDS gene fragment hypermethylation in chronic high level of arsenic exposure with and without arsenic induced cancer. Springer Plus. 2013; 2:557.
- Tahara T, Shibata T, Nakamura M, Okubo M, Yamashita H, Yoshioka D, et al. Association between polymorphism in XRCC1 and GST genes and CpG island methylation status in colonic mucosa in ulcerative colitis. Virchows Acrh. 2011; 458:205–11.
- Liu R, Yin L, Pu Y, Li Y, Liang G, Zhang J, et al. Functional alteration in Glutathione S-Transferase Family associated with enhanced occurrence of esophageal carcinoma in China. J Toxicol Environ Health A. 2010; 73:471–82.
Abstract Views: 542
PDF Views: 0