title: Genotoxicity of dichlorvos in strains of Drosophila melanogaster defective in DNA repair.
abstract: Dichlorvos (DDVP), an organophosphate pesticide, is reported to be genotoxic at high concentrations. However, the roles of DNA damage repair pathways in DDVP genotoxicity are not well characterized. To test whether pre- and post-replication pathways are involved, we measured changes in DNA migration (Comet assay) in the midgut cells of Drosophila melanogaster Oregon R+ larvae and in some mutants of pre- (mei-9, mus201, and mus207) and post- (mei-41 and mus209)replication DNA repair pathways. Insects were exposed to environmentally relevant concentrations of DDVP (up to 15ng/ml) for 48h. After insect exposure to 0.15ng/ml DDVP, we observed greater DNA damage in pre-replication repair mutants; effects on Oregon R+ and post-replication repair mutants were insignificant. In contrast, significant DNA damage was observed in the post-replication repair mutants after their exposure to 1.5 and 15ng/ml DDVP. The pre-replication repair mutant mus207 showed maximum sensitivity to DDVP, suggestive of alkylation damage to DNA. We also examined mutants (SOD- and urate-null) that are sensitive to oxidative stress and the results indicate that significant oxidative DNA damage occurs in DDVP-exposed mutants. This study suggests involvement of both pre- and post-replication repair pathways against DDVP-induced DNA damage in Drosophila, with oxidative DNA damage leading to genotoxicity.
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, Uttar Pradesh, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Mishra
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, Uttar Pradesh, India.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, Uttar Pradesh, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Shukla
authors.affiliation: Analytical Section and Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, Uttar Pradesh, India.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, University of Lucknow, Lucknow 226007, Uttar Pradesh, India.
authors.forename: U N
authors.initials: UN
authors.lastname: Dwivedi
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, Uttar Pradesh, India. Electronic address: dkarchowdhuri@rediffmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Kar Chowdhuri
mesh_terms: D000818:Animals; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004006:Dichlorvos / Q000009:adverse effects* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D007306:Insecticides / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D007306:Insecticides; D004006:Dichlorvos
keywords: DNA damage; Dichlorvos; In vivo; Oxidative stress