Barranco S C, Flournoy D R
J Natl Cancer Inst. 1977 Mar;58(3):657-63. doi: 10.1093/jnci/58.3.657.
The survival and cell kinetics effect of 1,2:5,6-dianhydrogalactitol, NSC-132313 (galactitol), were studied on mammalian cells. Nondividing or plateau-phase cells were almost two times more sensitive to galactitol than were cells treated in the dividing state (dose required to reduce survival by 63% on the exponential part of the survival curve (DO)=4.2 mug/ml/hr for dividing cells vs. DO=2.4 mug/ml/hr in nondividing cells). The survival curves were characterized as having shoulder regions, followed by exponential decreases in survival as the drug doses were increased above 12 mug/ml for 1 hour. Synchronized mitotic and G1 phase cells were equally sensitive to galacitol, with approximately 90% of the cells killed by 1-hour exposures to 12.5 mug galactitol/ml. Cells in early S phase were the least sensitive to this drug dose (survival greater than 20%); however, the cells became more sensitive as they progressed through the S phase and into the G2 phase. There were no large differences observed in survival sensitivities anywhere in the cell cycle, suggesting that galactitol was not a cell-cycle phase-specific agent. Cells in mitosis or G1 phases of the cell cycle at the time of treatment with galacitol progressed normally into the next stage of the cell cycle; however, cells exposed to galactitol in S or G2 phases exhibited dose-dependent delays in those phases of the cell cycle. Nondividing cells exposed to high doses of galactitol could not recover from potentially lethal damage (PLD); however, nondividing cells exposed to lower galactitol doses (lethal dose to 10% of the cells) did exhibit slight recovery from PLD. Dividing cells did not recover from PLD at any of the doses tested. Both dividing and nondividing cells were more sensitive (cell kill) to galactitol when it was administered in two dose fractions 4-8 hours apart than when the same total integral dose was given as a single exposure. A 25-50% greater cell kill was achieved in nondividing cell populations given two dose fractions versus a single exposure to galactitol. Up to 60% greater cell kill was obtained with fractionalated doses in dividing cell populations. These responses to fractionated dose treatments were also dose-dependent.
对1,2:5,6 - 二脱水半乳糖醇（NSC - 132313，半乳糖醇）对哺乳动物细胞的存活及细胞动力学效应进行了研究。静止期或平台期细胞对半乳糖醇的敏感性几乎是处于分裂期细胞的两倍（存活曲线指数部分使存活降低63%所需剂量（DO）：分裂期细胞为4.2微克/毫升/小时，而静止期细胞为2.4微克/毫升/小时）。存活曲线的特征是有肩区，当药物剂量在1小时内增加到12微克/毫升以上时，存活呈指数下降。同步化的有丝分裂期和G1期细胞对半乳糖醇同样敏感，1小时暴露于12.5微克半乳糖醇/毫升时约90%的细胞被杀死。早期S期细胞对该药物剂量最不敏感（存活率大于20%）；然而，随着细胞进入S期并进入G2期，它们变得更敏感。在细胞周期的任何位置观察到的存活敏感性没有大的差异，这表明半乳糖醇不是细胞周期阶段特异性药物。在用半乳糖醇处理时处于有丝分裂期或细胞周期G1期的细胞正常进入细胞周期的下一阶段；然而，在S期或G2期暴露于半乳糖醇的细胞在这些细胞周期阶段表现出剂量依赖性延迟。暴露于高剂量半乳糖醇的静止期细胞无法从潜在致死损伤（PLD）中恢复；然而，暴露于较低半乳糖醇剂量（使10%细胞致死的剂量）的静止期细胞确实从PLD中表现出轻微恢复。在任何测试剂量下，分裂期细胞都不能从PLD中恢复。当以间隔4 - 8小时的两个剂量分次给药时，分裂期和静止期细胞对半乳糖醇都更敏感（细胞杀伤），而不是给予相同的总累积剂量单次暴露时。与单次暴露于半乳糖醇相比，给静止期细胞群体两个剂量分次可实现25 - 50%更大的细胞杀伤。在分裂期细胞群体中，分次剂量可实现高达60%更大的细胞杀伤。这些对分次剂量处理的反应也是剂量依赖性的。
