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Carcinogen-induced Drug Resistance in Rat Hepatocytes¹

McArdle Laboratory for Cancer Research [B. I. C., B. A. L.] and Wisconsin Clinical Cancer Center [B. I. C.], University of Wisconsin Center, Madison, Wisconsin 53706

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 rats 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.

¹ This investigation was supported by Grants CA-07175, CA-24818, and P01-CA-20432 awarded by the National Cancer Insitute, Department of Health, Education, and Welfare.

² Present address: Dept. of Medical Oncology, City of Hope National Medical Center, 1500 E. Duarte Rd., Duarte, Calif. 91010. To whom requests for reprints should be addressed.

³ Research Scholar of the Foundation for Cancer Research, Chicago.

Received 7/28/80. Accepted 1/30/81.

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