title: Influence of CYP2C9, GSTM1, GSTT1 and NAT2 genetic polymorphisms on DNA damage in workers occupationally exposed to organophosphate pesticides.
abstract: Previous studies have revealed that organophosphate pesticides (OPs) are primarily metabolized by xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticides-exposed workers. Present study was designed to determine the influence of CYP2C9, GSTM1, GSTT1 and NAT2 genetic polymorphisms on DNA damage in workers occupationally exposed to OPs. We examined 268 subjects including 134 workers occupationally exposed to OPs and an equal number of normal healthy controls. The DNA damage was evaluated using alkaline comet assay and genotyping was done using individual polymerase chain reaction (PCR) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Acetylcholinesterase and paraoxonase activity were found to be significantly lowered in workers as compared to control subjects which were analyzed as biomarkers of toxicity due to OPs exposure (p<0.001). Workers showed significantly higher DNA tail moment (TM) compared to control subjects (14.32±2.17 vs. 6.24±1.37 tail % DNA, p<0.001). GSTM1 null genotype was found to influence DNA TM in workers (p<0.05). DNA TM was also found to be increased with concomitant presence of NAT2 slow acetylation and CYP2C9*3/*3 or GSTM1 null genotypes (p<0.05). DNA TM was found increased in NAT2 slow acetylators with mild and heavy smoking habits in control subjects and workers, respectively (p<0.05). The results of this study suggest that GSTM1 null genotypes, and an association of NAT2 slow acetylation genotypes with CYP2C9*3/*3 or GSTM1 null genotypes may modulate DNA damage in workers occupationally exposed to OPs.
authors: Division of Biochemistry & Biotechnology, National Centre for Disease Control, 22, Sham Nath Marg, Delhi 110054, India. satyenders@gmail.com
authors: Satyender
authors: S
authors: Singh
authors: Vivek
authors: V
authors: Kumar
authors: Priyanka
authors: P
authors: Singh
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; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D020552:Comet Assay; D065729:Cytochrome P-450 CYP2C9; D004249:DNA Damage; 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
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D001191:Arylamine N-Acetyltransferase; D065729:Cytochrome P-450 CYP2C9; D005982:Glutathione Transferase; D009943:Organophosphorus Compounds; D010575:Pesticides; C450260:CYP2C9 protein, human; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1