title: Genetic polymorphisms of GSTM1, GSTT1 and GSTP1 and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides.
abstract: GSTM1, T1 and P1 are important enzymes of glutathione S-transferases (GSTs), involved in the metabolism of many endogenous and exogenous compounds. Individual genetic variation in these metabolizing enzymes may influence the metabolism of their substrates. The present study was designed to determine the genotoxic effects using DNA damage and its association with GSTM1, GSTT1, and GSTP1 (Ile105Val) genetic polymorphisms in workers occupationally exposed to organophosphate pesticides (OPs). We examined 230 subjects including 115 workers occupationally exposed to OPs and an equal number of normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using individual PCR or PCR-RFLP. Significantly higher DNA tail moment (TM) was observed in workers as compared to control subjects (14.41 ± 2.25 vs. 6.36 ± 1.41 tail % DNA, p<0.001). The results revealed significantly higher DNA TM in workers with GSTM1 null genotype than those with GSTM1 positive (15.18 vs. 14.15 tail % DNA, p=0.03). A significantly higher DNA TM was also observed in workers with homozygous Ile-Ile GSTP1 genotype than heterozygous (Ile-Val) and mutant (Val-Val) GSTP1 genotype (p=0.02). In conclusion, the results show that null deletion of GSTM1 and homozygote wild GSTP1 genotype could be related to inter-individual differences in DNA damage arises from the gene-environment interactions in workers occupationally exposed to OPs.
authors: Division of Biochemistry and Biotechnology, National Centre for Disease Control, 22, Sham Nath Marg, Delhi 110054, India.
authors: Satyender
authors: S
authors: Singh
authors: Vivek
authors: V
authors: Kumar
authors: Priyanka
authors: P
authors: Singh
authors: Sachin
authors: S
authors: Thakur
authors: Basu Dev
authors: BD
authors: Banerjee
authors: Rajender Singh
authors: RS
authors: Rautela
authors: Shyam Sunder
authors: SS
authors: Grover
authors: Devendra Singh
authors: DS
authors: Rawat
authors: Syed Tazeen
authors: ST
authors: Pasha
authors: Sudhir Kumar
authors: SK
authors: Jain
authors: Arvind
authors: A
authors: Rai
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D020552:Comet Assay; D004249:DNA Damage; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*; D011110:Polymorphism, Genetic; D012907:Smoking
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D009943:Organophosphorus Compounds; D010575:Pesticides; C413545:glutathione S-transferase T1