N-glucuronide formation of carcinogenic aromatic amines in rat and human liver microsomes.
(1) Sensitive fluorimetric assays were developed for the determination of microsomal UDP-glucuronosyltransferase activities towards 1- and 2-naphthylamine and 4-aminobiphenyl. (2) In rat liver microsomes, enzyme activity towards 1-naphthylamine was orders of magnitude higher than the activities towards 2-naphthylamine, 4-aminobiphenyl or aniline. The differences were less marked with human liver microsomes. (3) Glucuronidation of aniline and 4-aminobiphenyl was not appreciably altered in rat liver microsomes from 3-methylcholanthrene- or phenobarbital-treated rats. UDP-glucuronosyltransferase activities towards 1- and 2-naphthylamine were selectively increased (about 2-fold) by 3-methylcholanthrene-treatment. However the increases were less marked than those observed with representative substrates of the 3-methylcholanthrene-inducible enzyme form. The results suggest that the arylamines investigated are predominantly conjugated by constitutive enzyme forms in rat liver. (4) Arylamine N-glucuronides were found to be susceptible to hydrolysis by E. coli beta-glucuronidase suggesting the release of carcinogenic arylamines in the gut and their enterohepatic circulation.
D015057:1-Naphthylamine / Q000378:metabolism; D015081:2-Naphthylamine / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D000611:Aminobiphenyl Compounds / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005965:Glucuronates / Q000378:metabolism*; D005966:Glucuronidase / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000032:analysis; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D005965:Glucuronates; D015057:1-Naphthylamine; D015081:2-Naphthylamine; D014453:Glucuronosyltransferase; D005966:Glucuronidase