EFFECT OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE ON CELL VIABILITY, DNA-SYNTHESIS, AND CHROMATID BREAKAGE IN SYNCHRONIZED HAMSTER FIBROSARCOMA CELLS

Abstract

Hamster fibrosarcoma cells were synchronized by mitotic selection and exposed to varying concentrations of 1-.beta.-D-arabinofuranosylcytosine (ara-C) for 2 h in mid-S phase. There was a direct relationship between DNA synthesis inhibition and cytotoxicity produced by ara-C once DNA synthesis was decreased by over 85%. The noncytotoxic concentration of 10-5 M ara-C produced little chromatid breakage; but extensive chromatid breakage and chromosomal rearrangement were seen in cells treated with the cytotoxic concentration of 10-3 M ara-C, supporting earlier observations that chromatid breakage is correlated with cytotoxicity. Predominantly small DNA was synthesized when cells were treated with 10-5 and 10-3 M ara-C, and this DNA could be completely chased into high MW DNA after addition of deoxycytidine. Both concentrations of ara-C also inhibited, to different degrees, the joining of intermediate size DNA fragments into larger DNA. Neither parameter appeared directly related to the ara-C produced cytotoxicity.