Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver.
1. Enzymic azoreduction of the hepatocarcinogen, N,N-dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4'-hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4'-hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy. 2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4'-hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro. 3. Treatment with clofibrate of beta-naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4'-hydroxy-DAB. Triiodothyronine, which induces 4'-nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4'-hydroxy-DAB UDP-GT activity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D001711:Biotransformation; D004790:Enzyme Induction; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000378:metabolism; D006498:Hepatectomy; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism; D009601:Nitroreductases; D051381:Rats; D011911:Rats, Gunn; D011919:Rats, Inbred Strains; D004124:p-Dimethylaminoazobenzene / Q000378:metabolism* / Q000494:pharmacology
D001391:Azo Compounds; D005965:Glucuronates; D004124:p-Dimethylaminoazobenzene; D009247:NADH, NADPH Oxidoreductases; D009601:Nitroreductases; C021106:azoreductase; D014453:Glucuronosyltransferase