Association of GSTM1 and GSTT1 Gene Deletions with Susceptibility to DNA Damage in the Pesticide-Exposed Workers of Punjab

Abstract

The main aim of this study was to evaluate genotoxic effects of pesticides in association with glutathione S-transferase (GST) polymorphism. To achieve this aim, DNA damage and the genotypes of the GSTM1 and GSTT1 genes were studied from blood lymphocytes of pesticide-exposed and unexposed (control) agricultural workers of the Punjab region of northwestern India. The blood samples were collected from 40 exposed and 27 unexposed subjects from the Kakrala and Sanour villages of Patiala district. DNA damage was evaluated by using an alkaline comet assay. The analysis of the comets was done through visual scoring and image analysis software (Tritek's CometScore). Damage Index (DI), Damage Frequency (DF) (calculated by visual scoring method), and % DNA in tail (measured by image analysis software) were considered for assessing DNA damage. The DNA extraction from blood cells was done using proteinase K and the phenol-chloroform method, and genotyping of GSTM1 and GSTT1 was done using multiplex PCR. It was found that all the pesticide-exposed subjects showed higher DI, DF, and % DNA in tail in comparison to the controls. The statistical comparison of DNA damage between the exposed group and unexposed group revealed highly significant differences (p < 0.05; Mann-Whitney U-test). In addition, the GSTT1 gene deletion and simultaneous deletions of GSTM1 and GSTT1 genes in increasing DNA damage were observed in the exposed group.

DNA variants and organophosphate neurotoxicity among emerging farmers in the Western Cape of South Africa

“…Previous studies investigating the role of the GST enzymes have produced inconsistent results. Abhishek et al 26 found that GSTT1 modified OP exposure and DNA damage but not Singh et al 3,19 The prevalence null allele of GSTT1 (< 2%) in our population was, however, low. Previous epidemiological studies have found that the rs854560 (PON1) variant played a role in the modification of OP neurotoxicity.…”

“…In three of the four studies that investigated the effect of GST on OP neurotoxicity, the GSTM1 null genotype was associated with increased DNA damage, 13,18,19,26 but there have not been studies on neurotoxicity.…”

“…Genetic variants of the mu (GSTM1) and theta (GSTT1) group exist and are well documented in literature. 26 The variation in these enzymes is due to gene deletions resulting in null genotypes. Individuals with the null genotypes are suspected to be more susceptible to effects of OPs due to its reduced or absent metabolizing properties.…”

“…18,27 Four epidemiological studies have been conducted to determine whether GST (GSTM1 and GSTT1) and NAT2 DNA variants modify OP neurotoxicity and the results differ between these studies. In India, Abhishek et al 26 found that GSTT1 played a key role in OP susceptibility but GSTM1 had no effect on DNA damage. The OP exposed individuals, with the GSTT1 null genotype showed higher DNA damage compared to those with the GSTT1 gene, present.…”

Assessment of Individual Susceptibility to Baseline DNA and Cytogenetic Damage in a Healthy Turkish Population: Evaluation with Lifestyle Factors

“…After Collins et al (1993) have modified the comet assay with specific endonucleases, we conducted a small-sized study to investigate the role of some polymorphic genes and oxidative DNA damage (detected with a modified comet assay) in Barrett's esophagus patients and found no association for the GSTM1 gene (Kadioglu et al, 2010). However, some recent studies on environmental exposures or cigarette smoking found an influence of the GST genotypes on the comet assay (Abhishek et al, 2010;Lee et al, 2010). Contrary to our expectations, no correlation between lifestyle factors and MN, CAs, or BLM-induced CA frequencies was observed in the present study.…”