TY - JOUR
T1 - Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver
AU - Raza, H.
AU - Levine, W. G.
AU - Chowdhury, N. Roy
AU - Chowdhury, J. Roy
N1 - Funding Information:
This work was supported in part by National Institutes of Health grants CA 14231, CA 13330. AM 34357, AM 2019 and AM17702. J. R. C. is a recipient of a Research Career Development Award (AM 1016) of the National Institutes of Health.
PY - 1987
Y1 - 1987
N2 - 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 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. 4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4'hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.
AB - 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 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. 4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4'hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.
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U2 - 10.3109/00498258709043974
DO - 10.3109/00498258709043974
M3 - Article
C2 - 3114967
AN - SCOPUS:0023177872
SN - 0049-8254
VL - 17
SP - 669
EP - 677
JO - Xenobiotica
JF - Xenobiotica
IS - 6
ER -