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Persistently Increased Expression of a 3-Methylcholanthrene-inducible Phenol Uridine Diphosphate-Glucuronosyltransferase in Rat Hepatocyte Nodules and Hepatocellular Carcinomas¹

Institute of Toxicology, University of Tübingen, Wilhelmstrasse 56, Tübingen, D-7400 Federal Republic of Germany [K. W. B., P. A. M., E. R., D. S.], and Department of Pathology, Huddinge Hospital, S-14186 Huddinge, Sweden [L. C. E.]

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 M_r 55,000 polypeptide corresponding to the previously characterized UDP-GTI or phenol UDP-GT. However, in some hepatocyte nodules and hepatocellular carcinomas either the M_r 55,000 or a new M_r 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.

¹ Supported by the Deutsche Forschungsgemeinschaft and the Swedish Medical Research Council.

² To whom requests for reprints should be addressed.

Received 12/29/89. Revised 2/19/90.

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