title: Effects of piperonyl butoxide on dimethylnitrosamine metabolism and toxicity in Swiss mice.
abstract: The effects of piperonyl butoxide (PB) on the metabolism and toxicity of dimethylnitrosamine (DMN) in Swiss mice were determined. PB, at doses of 10 and 20 mg/kg, inhibited DMN demethylase 45 min after treatment by 18 and 37%. These inhibitory effects were marked 0.5 hr after PB (640 mg/kg) treatment and reached maximal effects at 2 hr when there was 55% inhibition of enzyme activity. The inhibition by PB continued for 24 hr where enzyme activity was suppressed by 35%. At 48 hr after treatment there was stimulation of enzyme activity. Enzyme kinetic determinations showed no change in Km but Vmax decreased from 129 to 49 mumol CH2O/min-g liver. PB (640 mg/kg) inhibited DMN (500 mg/kg; im) mutagenicity in the host-mediated assay, decreasing the mutant frequency by 42%. Paradoxically, PB (640 mg/kg) had no effect on the alkylation of nucleic acids or proteins in mouse liver, kidney, lung, or spleen. In addition, pretreatment with PB (640 mg/kg) had no effect on the LD50 of DMN.
mesh_terms: D000478:Alkylation; D000818:Animals; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000633:toxicity*; D007928:Lethal Dose 50; D008099:Liver / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009153:Mutagens / Q000494:pharmacology; D009602:Nitrosamines / Q000633:toxicity*; D010882:Piperonyl Butoxide / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D009153:Mutagens; D009602:Nitrosamines; D008780:Methyltransferases; D010882:Piperonyl Butoxide; D004128:Dimethylnitrosamine