Enhanced drug-metabolizing capacity within liver adjacent to human and rat liver tumors.

Abstract

Cytochrome P-450 content (nmol/g of liver) differed within regions of rat liver according to proximity to intrahepatically implanted Morris hepatoma 7795 or 5123D. Liver adjacent to tumor had higher microsomal cytochrome P-450 content, decreased DNA content (mg/g of liver) and unaltered cytochrome c reductase activity compared to histologically indistinguishable liver far-removed from the tumor. Liver adjacent to or far-removed from tumor contained markedly more cytochrome P-450 and higher cytochrome c reductase activity but less DNA than transplanted Morris hepatomas 7795 and 5123D that were grown intrahepatically. Compared to i.m. implants of these same tumors, intrahepatically implanted Morris hepatomas 7795 and 5123D had increased cytochrome P-450 content. Tumor-containing liver from 2 human subjects revealed regional changes in cytochrome P-450-mediated monooxygenases similar to those observed in rats. Histomorphically nontumorous mammalian liver directly adjacent to intrahepatic tumors exhibits previously unsuspected biochemical alterations.