[The role of UDP glucuronosyl- and sulfotransferases in the butylhydroxytoluene suppression of the mutagenic action of carcinogenic nitroso compounds and cyclophosphane].
Treatment with butylated hydroxytoluene (BHT) was shown to stimulate the activity of UDP-glucuronosyltransferase and to inhibit that of sulfotransferase in liver of Wistar male rats. Addition of UDP-glucuronic acid to incubation medium in Ames' test using BHT-pretreated subfractions of rat liver resulted in decreased mutagenicity of nitrosodiethylamine, nitrosomorpholine and cyclophosphamide. Further treatment with 3'-phosphoadenosine-5'-phosphosulfate failed to affect mutagenic activity of the promutagens tested. However, an increase in mutagenicity of nitrosomorpholine and cyclophosphamide was observed in application of liver subfractions from intact animals. It was concluded that BHT-induced inhibition of active metabolite production as well as increased production of their glucuronides are responsible for inhibition of mutagenicity of the agents tested. Simultaneous decrease in the yield of sulfates potentiated this effect for nitrosomorpholine and cyclophosphamide.
Kalinina
E V
EV
Loknitskaia
N N
NN
Shuliakovskaia
T S
TS
Fonshteĭn
L M
LM
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D004347:Drug Interactions; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests; D009154:Mutation; D009603:Nitroso Compounds / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D015238:Sulfotransferases / Q000378:metabolism*
D009603:Nitroso Compounds; D002084:Butylated Hydroxytoluene; D003520:Cyclophosphamide; D014453:Glucuronosyltransferase; D015238:Sulfotransferases
O roli UDF-gliukoronozil- i sul'fotransferaz v podavlenii butilgidroksitoluolom mutagennogo deĭstviia kantserogennykh nitrozosoedineniĭ i tsiklofosfana.