Abstract
Hamster fibrosarcoma cells were synchronized by mitotic selection and exposed to varying concentrations of 1-β-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.
Original language | English (US) |
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Pages (from-to) | 3789-3797 |
Number of pages | 9 |
Journal | Cancer Research |
Volume | 36 |
Issue number | 10 |
State | Published - Oct 1976 |
ASJC Scopus subject areas
- Oncology
- Cancer Research