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A Genetic Approach to the Study of Cytotoxicity and Resistance of Cultured Chinese Hamster Cells in the Presence of Cytosine Arabinoside¹

Carcinogenesis Program, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, and Department of Zoology and Entomology, The University of Tennessee, Knoxville, Tennessee 37916

The basis of sensitivity and resistance of various Chinese hamster cell lines to the synthetic nucleoside, cytosine arabinoside, was studied. This agent was found to have an inhibitory effect on both DNA and protein synthesis. There was a differential but inhibitory effect on the synthesis of histones and other proteins. Survival studies showed an increasing probability of death with dose and time of exposure, in agreement with the hypothesis that probable errors in protein synthesis or regulation result in the observed unbalanced growth and death of cells sensitive to cytosine arabinoside.

Studies of hybrids constructed from isolated resistant and sensitive cell lines showed that resistance is a recessive phenotype, and a case of interallelic complementation was found. A nucleoside diphosphate reductase enzyme(s) appears to be involved in the resistance to cytosine arabinoside of the resistant Chinese hamster cells investigated in this study.

¹ Research supported jointly by the National Cancer Institute and the United States Atomic Energy Commission under contract with Union Carbide Corporation. This is Paper IV in a series entitled "Mammalian Cell Genetics."

² Submitted manuscript to The University of Tennessee in partial fulfillment of requirements for the degree of Doctor of Philosophy in Zoology.

³ Present address: Department of Human Genetics, University of Michigan Medical School, 1137 East Catherine Street, Ann Arbor, Michigan 48104.

Received 12/ 8/71. Accepted 4/18/72.