title: ROS-dependent genotoxicity, cell cycle perturbations and apoptosis in mouse bone marrow cells exposed to formulated mixture of cypermethrin and chlorpyrifos.
abstract: Swiss albino mice were exposed to formulated cypermethrin (CMR) and/or or chlorpyrifos (CPF) through oral gavages for 60 days. Test doses of CMR (0.69, 1.38 or 2.76mg/kg/day) or CPF (0.5, 1.0 or 2.0mg/kg/day) or CMR + CPF (0.69 + 0.5, 1.38 + 1.0 or 2.76 + 2.0mg/kg/day) were based on the acute oral median lethal doses of CMR or CPF. Chromosome aberrations (CA), micronucleus (MN) induction, cell cycle perturbations, apoptosis and reactive oxygen species (ROS) generation were analysed in bone marrow cells. To explore the involvement of ROS induction, HaCat cells were exposed in vitro to arbitrary concentrations of CMR and/or CPF. Exposure of CMR (2.76mg/kg/day) induced significant inhibition of mitotic index. Significant (P < 0.01) frequencies of CA and MN were observed with the CMR at 1.38mg/kg/day, whereas CPF or its mixture CMR + CPF showed at highest doses. Chromosome/chromatid breaks and fragments were found to be major aberrations in all the treatment groups. Highest doses of CMR or CMR + CPF revealed significant (P < 0.01 or 0.001) elevation of G0/G1peak, while CPF-exposed cells revealed significant (P < 0.01) declined in G1phase. Decline in S phase was observed with highest dose of CMR only. Apoptosis induction measured by gating cell population beside G1peak showed 3- to 4-fold increase in apoptotic cells in CPF-exposed mice as compared to control or CMR or CMR + CPF-treated mice. Further, all the treatment groups in vivo as well as in vitro revealed significant generation of ROS in comparison with the control group. Present results, together with the earlier reports, which substantiate ROS generation may be major cause of genotoxicity, cell cycle perturbations and apoptosis, nonetheless co-exposure of low doses of CMR and CPF mixture does not potentiate genotoxicity.
authors.affiliation: Petroleum Toxicology Division.
authors.forename: Lalit K S
authors.initials: LK
authors.lastname: Chauhan
authors.affiliation: Petroleum Toxicology Division.
authors.forename: Meenu
authors.initials: M
authors.lastname: Varshney
authors.affiliation: Petroleum Toxicology Division.
authors.forename: Vibha
authors.initials: V
authors.lastname: Pandey
authors.affiliation: Petroleum Toxicology Division.
authors.forename: Preeti
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Petroleum Toxicology Division.
authors.forename: Vipin K
authors.initials: VK
authors.lastname: Verma
authors.affiliation: Animal Facility, Indian Institute of Toxicology Research, PO Box-80, Mahatma Gandhi Road, Lucknow 226 001, Uttar Pradesh, India.
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Petroleum Toxicology Division, sudhir.ji@gmail.com.|Present address: Department of Biochemistry, All India Institute of Medical Sciences Bhopal, Saket Nagar, Bhopal 462024, Madhya Pradesh, India.
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Goel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D004390:Chlorpyrifos / Q000494:pharmacology / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D007306:Insecticides / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D011722:Pyrethrins / Q000494:pharmacology / Q000633:toxicity*; D017382:Reactive Oxygen Species
chemical_list: D007306:Insecticides; D011722:Pyrethrins; D017382:Reactive Oxygen Species; C017160:cypermethrin; D004247:DNA; D004390:Chlorpyrifos