Alkylation of guanine in mice in vivo by organophosphorus insecticides. I. Trichlorphone and butonate

Following intraperitoneal administration to male mice of trichlorphone, 4 mg/animal = 160 mg/kg and butonate, 5 and 10 mg/animal = 200 and 400 mg/kg, labeled by ¹⁴C in the OCH₃-groups, nucleic acids taken from different organs and urine were analyzed for 7-¹⁴C]methylguanine. The limit of detection was 2 × 10^?8, calculated as ¹⁴C relative to the total dose. The maximum of ¹⁴C in 7-methylguanine was 2 × 10^?7 in lung, kidney, and testicles and 3 × 10^?6 in liver. The excretion rate of 7-MeG from nucleic acids is very rapid, a halflife of 2.0 hr was measured in liver from butonate and of < 24 hr was calculated in the whole body from trichlorphone, contrary to the excretion rate of 3.0–3.5 days following administration of strongly genotoxic agents. The relative amounts of 7-¹⁴C]methylguanine excreted in the urine were determined and compared with data for dichlorvos, dimethyl sulfate, and methyl methanesulfonate from the literature. Following intraperiotoneal administration, the methylating capability towards N-7 of guanine in nucleic acids is given by the ratio of about 100:10:25 for dichlorvos, butonate, and trichlorphone, respectively.