Rat
ascites hepatoma (AH) cell lines that were induced by
dimethylaminoazobenzene and established as transplantable
tumors had different sensitivities to
vinblastine (VBL). The most VBL-resistant cells, AH66, showed more cross-resistance to
vincristine and
anthracyclines than AH66F cells. The resistance of AH66 cells was significantly decreased by
verapamil. VBL-resistance of AH66 cells was inhibited by other drugs reported as overcoming acquired multidrug resistance, while the sensitivity of AH66F cells was hardly influenced by these drugs. The lowered uptake and enhanced extrusion of the
antitumor drug in AH66 cells were suppressed by
verapamil. M(r) 160,000
protein in the plasma membrane from AH66 was labeled with a photoactive VBL analog and was immunopositive to a
monoclonal antibody against
P-glycoprotein, C219. The sensitive cells had barely detectable levels of the surface membrane components. Specific photo-labeling with a VBL analog of
P-glycoprotein of AH66 cell membrane was inhibited by
reserpine and
verapamil which restored the VBL resistance. These results indicate that AH66 cells are a naturally acquired multidrug-resistant cell line overexpressing a
P-glycoprotein, and AH cell lines are useful to study multidrug resistance of hepatic
carcinomas and development of counteracting drugs.