Heterogeneous alterations of UDP-glucuronosyltransferases in mouse hepatic foci

Abstract

UDP-glucuronosyltransferase (UDPGT) was studied immunohistochemically in hepatic foci and nodules of N-nitrosomorpholine-treated mice. Serial sections were stained for glucose-6-phosphatase (G6Pase). It was found that a high percentage of G6Pase-negative liver foci and nodules were also UDPGT-negative (34%). In addition, G6Pase-negative foci without altered UDPGT phenotype (30%) and UDPGT-negative foci without altered G6Pase phenotype (8%) were detected. G6Pase-positive foci were also present (24%). Interestingly, most G6Pase-positive foci were UDPGT-positive (16%). Some G6Pase-positive lesions without altered UDPGT phenotype were also found (8%). The major phenotype observed in rat hepatocarcinogenesis models (UDPGT-positive/G6Pase-negative foci) was not detectable in the mouse model. These results demonstrate heterogeneous alterations of UDPGTs in mouse hepatic foci. They furthermore suggest marked differences between the mouse and the rat in the regulation of UDPGTs in similarly induced rat hepatic foci.