[Butylhydroxytoluene inhibition of the mutagenic activity of carcinogenic nitroso compounds and cyclophosphamide: the role of the glutathione conjugation reaction].
Mutagenic effect of diethylnitrosamine, nitrosomorpholine and cyclophosphamide were studied on Salmonella typhimurium in the Ames test using S9, microsomal and cytosolic subfractions of Wistar male rats. Pretreatment with butylhydroxytoluene (BHT) was followed by a 50-60% decrease in metabolic activation of the said promutagens by liver subfractions. This was matched by an increase in cytosolic and microsomal glutathione-S-transferase activity and glutathione level in rat liver. The addition of glutathione to the incubation medium in the Ames test using liver subfractions of BHT-treated rats brought on a complete inhibition of mutagenic effect of the agents studied. It is suggested that BHT-induced decrease in production of active metabolites and increase in their inactivation in reactions of glutathione enzymatic conjugation account for the inhibition of mutagenicity of the promutagens under study.
Kalinina
E V
EV
Loknitskaia
N N
NN
Shuliakovskaia
T S
TS
Fonshteĭn
L M
LM
D000818:Animals; D001711:Biotransformation; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics; D009603:Nitroso Compounds / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D011355:Prodrugs / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000235:genetics
D009153:Mutagens; D009603:Nitroso Compounds; D011355:Prodrugs; D002084:Butylated Hydroxytoluene; D003520:Cyclophosphamide; D005978:Glutathione
Podavlenie butilgidroksitoluolom mutagennogo deĭstviia kantserogennykh nitrozosoedineniĭ i tsiklofosfana: rol' reaktsiĭ kon''iugatsii s glutationom.