Modulation of the GSTT1 activity by the GSTM1 phenotype in a sample of Italian farm-workers

Glutathione S-transferase (GST) isozymes catalyze nucleophilic attack by reduced Glutathione (GSH) on a variety of electrophilic compounds and play a central role in biotransformation of xenobiotics (Hayes et al., Annu Rev Pharmacol Toxicol 45:51-88, 2005). We performed a case-control study to evaluate the GSTM1 and GSTT1 polymorphisms and to investigate if exposure to pesticides conditions the GSTT1 activity level in 115 healthy controls and 90 farm-workers exposed to pesticides. Polymorphisms were investigated using a GSTM1 or a GSTT1-specific PCR. Enzyme activity was measured by means of DCM as co-substrate, as described by Bruhn et al. (Biochem Pharmacol 56:1189-1193, 1998). There was no significant difference between the farm-workers and the healthy controls regarding the distribution of various alleles of the GSTM1 and GSTT1 genes and the GSTT1 enzyme activity. In farm-workers, the GSTM1 null genotype was associated with a significant increase of GSTT1 activity, suggesting a regulative mechanism common to GSTM1 and GSTT1 enzymes after exposure to xenobiotics.