WOODCHUCK P-GLYCOPROTEIN FOUND IN VIRUS-INDUCED HEPATOCELLULAR CARCINOMAS BINDS ANTICANCER DRUGS

Virally-induced hepatocellular carcinomas (HCC) are intrinsically resi stant to cancer chemotherapy partly due to increased expression of p-g lycoprotein (pgp). In this study, we determined that pgp expressed in woodchuck HCC had binding properties were similar to the drug resistan t human pgp. Pgp drug binding properties were characterized by photoaf finity labeling with the calcium channel blocker [H-3]azidopine (AZD). AZD bound pgp in HCC but not in non-tumor liver samples, and binding was confirmed by competition with Adriamycin (IC50 = 10 mu M) and acti nomycin D (IC50 = 1 mu M). In summary, WHV-induced HCC overexpress a p gp which binds anticancer drugs suggesting a common pathway for drug r esistance.