Effect of the <i>GSTM1</i> Null Genotype on Glutathione S-Transferase (GST) Activity in Patients with Non-Viral Liver Tumors

Abstract

Glutathione S-transferase GST is a major phase II drug-metabolizing enzyme. Several isoforms of human GST as well as different GST genetic polymorphisms are known, but limited data exists concerning the relationship between GST polymorphisms and GST activity using 1-chloro-2,4-dinitrobenzene in human liver. To resolve this query, we analyzed the genetic polymorphisms of four main GST isoforms GST mu 1 GSTM1 , GST theta 1 GSTT1 , GST alpha 1 GSTA1 , GST pi 1 GSTP1 and measured hepatic GST activity isolated from the same patients. We found that GSTM1 null individuals have signi cantly lower P 0.0082 GST activity compared with GSTM1 positive individuals. No signicant changes in GST activity were observed in individuals with GSTT1, GSTA1, and GSTP1 genotypes. Interestingly, the levels of GST activity exhibited were similar when compared with GSTA1 A/ A and GSTA1 A/ B, and GSTP1 A/ A and GSTP1 A/ B, respectively, if the genotype was GSTM1 null. Therefore, the genotypes of GSTA1 A/ B and GSTP1 A/ B individuals do not signi cantly affect the level of hepatic GST activity. An examination of the correlation between GST mRNA expression and GST activity subsequently revealed a signi cant correlation between GSTM1 mRNA levels and GST activity r 0.626, P 0.007. These data are expected to facilitate research on the prediction of ef cacy and safety of GSTM1 null-mediated drug metabolism and may establish whether genetic polymorphisms of the GST gene, speci cally GSTM1, can act as a biomarker.

CAMBIOS EN LA ACTIVIDAD DE ENZIMAS ANTIOXIDANTES DE Myriophyllum quitense EXPUESTA A ENDOSULFÁN A DIFERENTES TEMPERATURAS

“…Sin embargo, la sensibilidad al ES fue mayor en la GSTm, debido a que mostró una actividad incrementada a 5 µg/L ES. Esta mayor sensibilidad podría explicarse por la especificidad de las múltiples isoformas de GST involucradas en la respuesta a xenobióticos, la cual se ha demostrado que es especieespecífica y tiene como blanco un amplio espectro de compuestos electrofílicos (Coleman et al 1997, Fujimiya et al 2016.…”