The effect of 1-beta-D-arabinofuranosylcytosine on cell viability, DNA synthesis, and chromatid breakage in synchronized hamster fibrosarcoma cells.
1976; National Institutes of Health; Volume: 36; Issue: 10 Linguagem: Inglês
Autores
Peter A. Jones, Mary S. Baker, William F. Benedict,
Tópico(s)Biopolymer Synthesis and Applications
ResumoHamster fibrosarcoma cells were synchronized by mitotic selection and exposed to varying concentrations of 1-beta-D-arabinofuranosylcytosine (ara-C) for 2 hr 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, thus supporting earlier observations that chromatid breakage is highly correlated with cytotoxicity. Predominantly small DNA was synthesized when cells were treated with both 10(-5) and 10(-3) M ara-C, and this DNA could be completely chased into high-molecular-weight 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; thus neither parameter appeared directly related to the ara-C-produced cytotoxicity.
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