Carcinogen-induced drug resistance in rat hepatocytes.

The relative resistance of liver cells in primary monolayer cell culture to the cytocidal effects of methotrexate, Adriamycin, cycloheximide, or aflatoxin B1 was studied using cells derived from normal rats, rats subjected to two-thirds hepatectomy, or rat fed dietary carcinogen. Normal rat liver cells were highly sensitive to the toxic effects of methotrexate. Adriamycin, cycloheximide, and aflatoxin B1. In contrast, liver cells from carcinogen-treated rats were resistant to the toxic effects of these agents. Cells derived from rats at 24 hr post two-thirds hepatectomy were sensitive to Adriamycin but not to cycloheximide or aflatoxin B1.