Induction of somatic mutations but not methylated DNA adducts in λlacZ transgenic mice by dichlorvos

In order to examine the in vivo genotoxic activity of dichlorvos, λlacZ transgenic mice (Muta™Mouse) were treated i.p. with single (4.4 or 11 mg/kg) or multiple (5×11 mg/kg) doses of this agent and sacrificed 4 h or 14 days post-treatment for DNA adduct measurement or mutant frequency analysis, respectively. Neither methylated DNA adducts nor an increase in mutant frequency were detected in the bone marrow, white blood cells, liver, spleen, lung, brain and sperm cells after the single doses. However, following multiple dosing a statistically significant 3-fold increase in mutant frequency was observed in the liver, while a non-statistically significant increase was observed in the bone marrow. In contrast, dimethylsulphate, a model methylating agent, gave rise to detectable DNA adducts but no increase in mutant frequency following i.p. administration of single (30 mg/kg) or multiple (10×6 mg/kg) doses.