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Kinetics of 1-ß-D-Arabinofuranosylcytosine-induced Chromosome Breaks¹

Laboratory of Cellular Pharmacology, Division of Hematology, Department of Pediatrics, Children's Hospital of Los Angeles, and University of Southern California School of Medicine, Los Angeles, California 90054

1-ß-D-Arabinofuranosylcytosine, an effective inhibitor of DNA synthesis, induces chromatid breakage during the G₁, S, and G₂ phases of the mitotic cycle but not during M phase in Don-C hamster fibroblasts. Breakage was prevented by simultaneous addition of deoxycytidine and ara-C in G₁, S, and G₂. The maximum sensitivity to ara-C is during the latter half of S and the beginning half of G₂. Deoxycytidine added 30 min after ara-C decreased the number of chromosome breaks during the S phase but not during G₁ or G₂.

These results imply that the inhibition of DNA synthesis is intimately related to the genesis of chromatid breakage. Repair of these lesions require processes which are peculiar to S phase.

¹ This investigation was supported by USPHS Grants CA-01649 and CA-11050 and T-493 from the American Cancer Society and was presented in part at the Meeting of the Western Society for Pediatric Research, January 30, 1970.

² Present address: Department of Pediatrics, Albany Medical Center, Albany, N. Y. 12208.

³ Leukemia Society of America Scholar. To whom reprint requests should be sent at Children's Hospital of Los Angeles, 4650 Sunset Blvd., Los Angeles, Calif.

Received 3/ 9/70. Accepted 6/ 8/70.

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