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1-ß-D-Arabinofuranosylcytosine-induced Malignant Transformation of Hamster and Rat Cells in Culture¹

Department of Biochemical Oncology, Microbiological Associates, Bethesda, Maryland 20014, [R. E. K., S. A. K., P. J. P.] and Division of Hematology-Oncology, Department of Medicine, Children's Hospital of Los Angeles, and the USC School of Medicine, Los Angeles, California 90027 [W. F. B.]

The potent antileukemic chemotherapeutic drug, 1-ß-D-arabinofuranosylcytosine (ara-C), was observed to transform malignantly secondary hamster fetal cells as well as established rat cells in vitro.

Results indicated that: (a) hamster cells altered by treatment with ara-C are morphologically indistinguishable from cells transformed with benzo(a)pyrene; (b) the ara-C-induced transformation can be observed under conditions of little or no inhibition of DNA synthesis and little or no cytotoxicity; (c) the transformation can occur with only a 6-hr exposure to ara-C; and (d) the transformation of hamster cells seems to require cellular DNA synthesis, for cells in S phase are much more sensitive to ara-C-induced transformation than are G₁-arrested cells.

Representative transformed colonies of hamster and rat cells produced rapidly growing fibrosarcomas in inoculated newborn hamsters and rats, respectively. Control cells remained nontumorigenic.

¹ Supported in part by contracts from the Council for Tobacco Research, Contract NIH-70-2068 within the Virus Cancer Program, USPHS, and Grant CA 14226 from the NIH.

² Recipient of a Career Development Award, NIH.

Received 10/29/74. Accepted 5/ 9/75.