Global Advanced Research Journal of Medicine and Medical Sciences (GARJMMS) ISSN: 2315-5159
September 2018, Vol. 7(7), pp. 145-152
Copyright © 2018 Global Advanced Research Journals

 

Full Length Research Article

Polymorphisms GSTT1, GSTM1 and GSTP1 influence in magnitude of DNA damage induced by cyclophosphamide

Azalea Castro-Rodriguez1, Jorge Humberto Serment-Guerrero2, Fernando Mejia-Sanchez3 and Julieta Castillo-Cadena3*

1Facultad de Medicina, Universidad Autónoma del Estado de México. Paseo Colón esq. Jesús Carranza S/N. Toluca de Lerdo, México. C.P. 50100.
2Departamento de Biología, Instituto Nacional de Investigaciones Nucleares, La Marquesa, Estado de México, México.
3Centro de Investigación en Ciencias Médicas, Universidad Autónoma del Estado de México, Jesús Carranza No. 205, Col. Universidad, Toluca de Lerdo, México. C.P. 50130.

*Corresponding Author E-mail: jcastilloc@uaemex.mx

Accepted 24 September, 2018

Abstract

Cancer is one of the major causes of death worldwide and one of the factors associated with this is the therapeutic failure. Recently there has been an increasing interest in designing personalized therapies based on patient’s genotype. Glutathione–S-Transferase genes GSTT1, GSTM1 and GSTP1 genes help in detoxification of various genotoxic agents such as cyclophosphamide, an indirect alkylating agent that damages the chemical structure of DNA. It is widely used with other drugs in the treatment of various cancers. Determine whether the extent of DNA damage evaluated by the comet assay performed in vitro by cyclophosphamide in lymphocytes is modulated by polymorphisms of GSTT1, GSTM1 and GSTP1. Lymphocytes from 120 healthy donors were treated with a single concentration of cyclophosphamide and the extent of DNA damage was evaluated by a modified comet assay. Polymorphisms of GSTT1 and GSTM1 were identified by end-point polymerase chain reaction, while GSTP1 alleles were identified by PCR-RFLP. A great variability in the response to cyclophosphamide was found among individuals. Only 12 individuals from all the volunteer donors showed to have the complete wild genotype (GSTT1, GSTM1, GSTP1Ile/Ile105, Ala/Ala114) and coincidentally, this was the group with the lowest cyclophosphamide produced DNA damage. The differences in tail length between this “wild type group” and the other 11 genotypes recognized were statistically significant, suggesting a relation between GST genotype and cyclophosphamide induced DNA damage modulation.

Keywords: GSTT1, GSTM1, GSTP1, Comet assay, Cyclophosphamide, DNA damage

 

References

Abdel RSZ, El ZR, Anwar W, Au WW (1996). A multiplex PCR procedure for polymorphic analysis of GSTM1 and GSTT1 genes in population studies. Cancer. Lett. 107: 229–233.

Arencibia DF, Rosario LA, Morffi J, Curveco D (2009). Estrategias en las evaluaciones genotóxicas. Retel. 23: 23-40.

Au WW, Oh HY, Grady J, Salama SA, Heo MY (2001). Usefulness of genetic susceptibility and biomarkers for evaluation of environmental health risk. Environ. Mol. Mutagen. 37: 215–225.

Bolt HM, Their R (2006). Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology. Curr. Drug. Metab. 7: 613–628.

Chávez YA (2011). Diversidad e implicaciones de los polimorfismos de las enzimas glutatión S transferasas en la patogénesis del asma. Med. UNAB. 14: 48–57.

Custódio AC, Almeida LO, Pinto GR, Santos MJ, Almeida JR, Clara CA, Rey JA, Casartelli C (2010). GSTP1 Ile 105 Val polymorphism in astrocytomas and glioblastomas. Genet. Mol. Res. 9: 2328–2334.

Emadi A, Jones RJ, Brodsky R (2008). Cyclophosphamide and cancer: golden anniversary. Nat. Rev. Clin. Oncol. 6: 638.

García O, Mandina T (2005). DNA damage evaluated by the comet assay in lymphocytes of children with 137Cs internal contamination caused by the Chernobyl accident. Mutat. Res. 565: 191–197.

García ST, McQuillan A, Panasci L (1988). Correlation between the cytotoxicity of melphalan and DNA crosslinks as detected by the ethidium bromide fluorescence assay in the F1 variant of B16 melanoma cells. Biochem. Pharmacol. 37: 3189.

Garibay GJ, Mejia SF, Ramírez SJE, Flores MM, Castillo CJ (2015). Genotoxicand cytotoxic damage by cyclophosphamide and adriamycin as a response to treatment in breast cancer patients: Pilot study. J. Can. Ther. 6: 163-168.

Goekkurt E, Hoehn S, Wolschke C, Wittmer C, Stueber C, Hossfeld DK, Stoehlmacher J (2006). Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS) novel predictors for response and survival in gastric cancer patients. Br. J. Can. 94: 281–286.

Gonzalez AAM, Hennessy BTJ, Mills GB (2010). Future of personalized medicine in oncology: A Systems Biology Approach. J. Clin. Oncol. 28: 2777.

Hayes JD, Flanagan JU, Jowsey IR (2004). Glutathione transferases. Annu. Rev. Pharmacol. Toxicol. 45: 51–88.

Hayes JD, Strange RC (2000). Glutathione S-Transferase polymorphisms and their biological consequences. Pharmacol. 61: 154–166.

Henderson CJ, Wolf CR (2005). Disruption of the glutathione transferase Pi class genes. Methods Enzymol. 401: 116-135.

Mejia SF, Castillo CJ, Sánchez MJC (2013). Development and application in Mexican of a method for the identification of polymorphisms of GSTP1. JMMS. 4: 287–290.

Moore MJ (1991). Clinical pharmacokinetics of cyclophosphamide. Clin. Pharmacokinet. 20:194.

Mossallam GI, Abdel HTM, Samra MA (2006). Glutathione S-transferase GSTM1 and GSTT1 Polymorphisms in adult acute myeloid leukemia; its impact on toxicity and response to chemotherapy. J. Egypt Natl. Can. Inst. 18: 264–273.

Oliveira AL, Rodrigues FFO, Santos RE, Aoki T, Rocha MN (2010). GSTT1, GSTM1, and GSTP1 polymorphisms and chemotherapy response in locally advanced breast cancer. Genet. Mol. Res. 9: 1045–1053.

Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor B (1987). Human glutathione S-transferase Theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem. J. 276: 271–276.

Petros WP, Hopkins PJ, Spruill S, Broadwater G, Vredenburgh JJ, Colvin OM, Peters WP, Jones RB, Hall J, Marks JR (2005). Associations between drug metabolism genotype, chemotherapy pharmacokinetics, and overall survival in patients with breast cancer. J. Clin. Oncol. 23: 6117-6125.

Rossini A, Rapozo DCM, Amorim LMF (2002). Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population. Genet. Mol. Res. 1: 233–240.

Sharma A, Pandey A, Sharma S, Chatterjee I, Mehrotra R, Sehgal A, Sharma JK (2014). Genetic polymorphism of glutathione S-transferase P1 (GSTP1) in Delhi population and comparison with other global populations. Meta Gene. 2: 134–142.

Silva J, Freitas TRO, Marinho JR, Speit G, Erdtmann B (2000). An alkaline single-cell gel electrophoresis (comet) assay for environmental biomonitoring with native rodents. Genet. Mol. Biol. 23: 241-245.

Soto QO, Cabrera GP, Téllez TG, Barrera FJ, Juárez RA, Castillo CJ (2011). Relationship of polymorphisms of glutathione S-Transferase GSTT1 and GSTM1 with the response to chemotherapy in Mexican women with advanced breast cancer. J. Can. Ther. 3: 354-361.

Stanulla M, Schaffeier EAS (2005). GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute lymphoblastic leukemia. Int. J. Hematol. 81: 39–44.

Steimer W, Potter JM (2002). Pharmacogenetic screening and therapeutic drugs. Clin. Chim. Acta. 315: 137.

Valladares A, Hernández NG, Gómez FS, Curiel QE, Madrigal BE, Vergara MD, Martínez MS, Arenas ADJ (2006). Genetic expression profiles and chromosomal alterations in sporadic breast cancer in Mexican women. Cancer Genet. Cytogenet. 170: 147–151.

Wang J, Wang T, Yin GY, Yang L, Wang ZG, Bu XB (2015). Glutathione S-transferase polymorphisms influence chemotherapy response and treatment outcome in breast cancer. Genet. Mol. Res. 14: 11126–11132.

Xu S, Wang Y, Roe B, Pearson WR (1998). Characterization of the human class Mu glutathione S-transferase gene cluster and the GSTM1 deletion. J. Biol. Chem.  273: 3517–3527.

Zhong S, Zhou SF, Chen X, Chan SY, Chan E, Ng KY, Duan W, Huang M (2006). Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese. Eur. J. Pharm. Sci. 28: 77–85.

 

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