Hepatic Microsomal Preparations and Purified Rat Liver -Glucuronidation of Carcinogenic Aromatic Amines Catalyzed N
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چکیده
The .\-|>lururonidut ¡onof three carcinogenic aromatic amines (4-aminobiphenyL, a-naphthylamine, and 0-naphthylamine) was investigated in hepatic microsomal preparations from two rat strains. In preparations from Wistar rats, individual variability was observed for the glucuronidation of the arylamines. This variability correlated with high and low levels of 3a-hydroxysteroid UDP-glucuronosyltransferase (UDPGT) in hepatic microsomal preparations from Wistar rats. This individual vari ability was not observed in Sprague-Dawley rat hepatic microsomal preparations because hepatic 3a-hydroxysteroid UDPGT levels do not vary in this strain of rats. Five highly purified rat liver UDPGTs were investigated for their ability to catalyze the conjugation of the aromatic amines. Of the purified enzymes investigated, only 3a-hydroxysteroid UDPGT catalyzed the glucuronidation of 4-aminobiphenyl. a-Naphthylamine and 0-naphthylamine conjugations were catalyzed by 3a-hydroxysteroid, 17/8-hydroxysteroid, and 3-methylcholanthrene-inducible p-nitrophenol UDPGTs. The three aromatic amines did not serve as substrates for purified digitoxigenin monodigitoxoside or phenobarbital-inducible mor phine UDPGTs. The results show that /V-glucuronide formation can be catalyzed by UDPGT isofonns which also catalyze the formation of 0-glucuronides. In addition, variable levels of 3a-hydroxysteroid UDPGT in Wistar rat liver may have toxicological significance for substrates of this isoenzyme.
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