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

 

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