The effect of 1-beta-D-arabinofuranosylcytosine on cell viability, DNA synthesis, and chromatid breakage in synchronized hamster fibrosarcoma cells.
Hamster 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.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002842:Chromatids / Q000187:drug effects*; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000378:metabolism; D008938:Mitosis; D008970:Molecular Weight; D012513:Sarcoma, Experimental / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013942:Thymine Nucleotides / Q000096:biosynthesis
D004273:DNA, Neoplasm; D013942:Thymine Nucleotides; D003561:Cytarabine; D013936:Thymidine