ROS-dependent genotoxicity, cell cycle perturbations and apoptosis in mouse bone marrow cells exposed to formulated mixture of cypermethrin and chlorpyrifos.

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 /G1 peak, while CPF-exposed cells revealed significant (P < 0.01) declined in G1 phase. Decline in S phase was observed with highest dose of CMR only. Apoptosis induction measured by gating cell population beside G1 peak 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.