Persistently increased expression of a 3-methylcholanthrene-inducible phenol uridine diphosphate-glucuronosyltransferase in rat hepatocyte nodules and hepatocellular carcinomas.
Increased UDP-glucuronosyltransferase in rat hepatocyte nodules and hepatocellular carcinomas produced by feeding 2-acetylaminofluorene or N-nitrosomorpholine was studied using isozyme-selective substrates, antibodies, and DNA probes. UDP-glucuronosyltransferase (UDP-GT) activities toward 4-methylumbelliferone, 1-naphthol, and benzo[a]pyrene-3,6-quinol were reversibly increased by short term feeding of 2-acetylaminofluorene but were persistently increased in hepatocyte nodules and differentiated hepatocellular carcinomas. Immunoblot analysis revealed that short term feeding of 2-acetylaminofluorene increased a Mr 55,000 polypeptide corresponding to the previously characterized UDP-GTI or phenol UDP-GT. However, in some hepatocyte nodules and hepatocellular carcinomas either the Mr 55,000 or a new Mr 53,000 polypeptide was preferentially increased, suggesting heterogeneous UDP-GT forms in liver nodules and carcinomas. Northern blot hybridization with a synthetic DNA probe to phenol UDP-GT demonstrated increased levels of mRNA in liver nodules. The results suggest persistently increased expression of at least two phenol UDP-GT enzyme forms in hepatocyte nodules, which may contribute to the toxin-resistance phenotype frequently observed at cancer prestages.
Bock
K W
KW
Institute of Toxicology, University of Tübingen, Federal Republic of Germany.
Münzel
P A
PA
Röhrdanz
E
E
Schrenk
D
D
Eriksson
L C
LC
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D000906:Antibodies; D012333:RNA, Messenger; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D014453:Glucuronosyltransferase