Momparler R L, Goodman J
Cancer Res. 1977 Jun;37(6):1636-9.
The in vitro effect of 5-aza-2'-deoxycytidine (5-aza-CdR) on cytotoxicity and macromolecular synthesis in A(T1)C1-3 hamster fibrosarcoma cells was investigated. The in vitro concentrations that produce 50% cell kill for 5-aza-CdR were about 1.0 and 0.01 microng/ml for a 2- and 24-hr exposure, respectively. 5-aza-CdR inhibited the growth of the fibrosarcoma cells by 40% at a concentration of 0.05 microng/ml. Deoxycytidine, but not cytidine, was a potent antagonist of the cytotoxicity produced by 5-aza-CdR. At cytotoxic concentrations 5-aza-CdR did not appear to inhibit DNA, RNA, or protein synthesis during a 1-hr incubation as measured by the incorporation of radioactive thymidine, uridine,, or leucine into acid-insoluble material. At a concentration of 10 microng/ml, 5-aza-CdR stimulated the incorporation of radioactive thymidine into DNA by more than 50%. These results indicate that 5-aza-CdR is a very potent cytotoxic agent to tumor cells in vitro at concentrations that do not inhibit macromolecular synthesis.
研究了5-氮杂-2'-脱氧胞苷（5-aza-CdR）对A(T1)C1-3仓鼠纤维肉瘤细胞的细胞毒性和大分子合成的体外作用。对于5-aza-CdR，2小时和24小时暴露产生50%细胞杀伤的体外浓度分别约为1.0和0.01微克/毫升。在浓度为0.05微克/毫升时，5-aza-CdR抑制纤维肉瘤细胞生长40%。脱氧胞苷而非胞苷是5-aza-CdR产生的细胞毒性的有效拮抗剂。在细胞毒性浓度下，通过将放射性胸苷、尿苷或亮氨酸掺入酸不溶性物质来测量，5-aza-CdR在1小时孵育期间似乎不抑制DNA、RNA或蛋白质合成。在浓度为10微克/毫升时，5-aza-CdR刺激放射性胸苷掺入DNA的量增加超过50%。这些结果表明，5-aza-CdR在不抑制大分子合成的浓度下是一种对肿瘤细胞非常有效的体外细胞毒性剂。
