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Hybridization of Actinomycin D- and Amethopterin-resistant Chinese Hamster Cells in Vitro¹

Division of Drug Resistance, Sloan-Kettering Institute for Cancer Research, New York, New York 10021

Hybrid cells were isolated from mixtures of two diploid strains of Chinese hamster cells maintained in vitro. One parent strain was highly resistant to amethopterin, had an increased level of dihydrofolate reductase activity, and was capable of forming tumors on heterotransplantation. The other parent strain, highly resistant to actinomycin D, had a low tumor-forming capacity and a low level of reductase. Karyotype analysis confirmed hybridization of these strains.

Studies of drug resistance and dihydrofolate reductase activity in cloned hybrid sublines indicated differences in the inheritance of resistance to amethopterin and to actinomycin D. Enzyme activity and resistance to amethopterin were intermediate between those of the parent strains, which suggested lack of interaction between the parental genomes. In contrast, resistance to actinomycin D appeared to be inherited as a dominant trait. Tumor-forming capacities of hybrid clones were as high and as low as or in between those of the parent strains.

¹ This investigation was supported in part by USPHS Research Grant CA 08748 and by American Cancer Society Grant T-107.

² Supported by the Ethel Darby Noble Fellowship Fund. Present address: Hasharon Hospital, Petach Tikvah, Israel.

³ Present address: Kinderklinik der Freien Universität, 1 Berlin 19, Germany.

⁴ To whom reprint requests should be sent at Sloan-Kettering Institute for Cancer Research, New York, N. Y. 10021.

Received 7/ 8/70. Accepted 11/16/70.