Cell cycle phase specificity of antitumor agents.

作者：Bishal Kumar Bhuyan, L G Scheidt, T J Fraser · 发表于：PubMed · 年份：1972 · 被引用次数：149 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Treatment and Pharmacology、Cancer therapeutics and mechanisms

Summary The sensitivity to drugs of synchronous and asynchronous populations of DON cells was studied. Agents that were cytotoxic at a specific phase of the cell cycle gave dose-survival curves that decreased to a constant saturation value. DNA synthesis inhibitors such as 1-β-d-arabinofuranosylcytosine, 5-azacytidine, 5-hydroxy-2-formylpyridinethiosemicarbazone (NSC 107392), sodium camptothecin (NSC 100880), 5-fluorodeoxyuridine, and pseudourea (NSC 56054) were most cytotoxic to cells in the S phase. However, the DNA synthesis inhibitor, neocarzinostatin, was most cytotoxic to cells in the G 1 phase. The protein synthesis inhibitors, pactamycin and sparsomycin, were also most cytotoxic to cells in the S phase. Cells in the G 1 -S border region were most sensitive to the RNA synthesis inhibitors, actinomycin D and nogalamycin, and to the alkylating agents, 1,3-bis(2-chloroethyl)-1-nitrosourea, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Streptozotocin and tubercidin, which markedly inhibit the synthesis of DNA, RNA, and protein, were cytotoxic to cells in all phase of the cell cycle. 5-Fluorouracil was also not phase specific. Cells in mitosis and in the G 1 phase were most sensitive to chlorambucil, l-phenylalanine mustard, and ellipticine.