Methotrexate cytotoxicity for L5178Y/Asn- lymphoblasts: relationship of dose and duration of exposure to tumor cell viability.
Methotrexate cytotoxicity for L5178Y/Asn- lymphoblasts: relationship of dose and duration of exposure to tumor cell viability.
复制标题
甲氨蝶呤对 L5178Y/Asn- 淋巴母细胞的细胞毒性：剂量和暴露时间与肿瘤细胞活力的关系。
作者：
D. Keefe;R. Capizzi;S. Rudnick
为了确定剂量和暴露时间对甲氨蝶呤（MTX）细胞毒性的相对贡献，将L5178 Y/Asn-小鼠白血病细胞的悬浮培养物暴露于0.1至100 μ M MTX 3至42小时。当暴露持续时间为3和6小时时，剂量和MTX细胞毒性之间存在线性关系（r = -0.66），而在暴露持续时间为18至42小时时，该曲线明显变平（r = -0.48）。此外，MTX细胞毒性与暴露6至42小时（剂量范围，1至100 μ M）的持续时间之间存在良好的相关性（r = -0.85）。使用线性最小二乘法，确定MTX细胞毒性动力学的最佳拟合方程为：log活力= 2.25 = 1.76（log持续时间）- 0.31（log剂量）。在实践中，该方程预测，暴露持续时间增加1个对数会导致细胞毒性增加近2个对数，而剂量增加1个对数只会导致细胞毒性增加0.3个对数。这些数据的临床效用表明，较低剂量MTX的长期输注与短期高剂量输注一样有用或更有用。
To determine the relative contribution of dose and duration of exposure to methotrexate (MTX) cytotoxicity, suspension cultures of L5178Y/Asn- murine leukemic cells were exposed to 0.1 to 100 microM MTX for 3 to 42 hr. Viability was determined by cloning in soft agar. While there was a linear relationship between dose and MTX cytotoxicity for exposure duration of 3 and 6 hr (r = -0.66), there was a pronounced flattening of this curve at exposure durations of 18 to 42 hr (r = -0.48). Furthermore, there was an excellent correlation (r = -0.85) between MTX cytotoxicity and durations of exposure for 6 to 42 hr (dose range, 1 to 100 microM). Using the linear least-squares method, a best-fit equation for the kinetics of MTX cytotoxicity was determined to be: log viability = 2.25 = 1.76 (log duration) - 0.31 (log dose). In practice, this equation predicts that a 1-log increase in duration of exposure results in almost a 2-log increase in cytotoxicity, whereas a 1-log increase in dose results in only a 0.3-log increase in cytotoxicity. The clinical utility of these data suggest that protracted infusions of lower doses of MTX would be equally as useful as or more useful than short-term high-dose infusions.
L1210 白血病细胞流出后甲氨蝶呤-聚谷氨酸盐的细胞外回收。
影响因子：
5.8
作者：
Poser,RG;Sirotnak,F;Chello,PL
通讯作者：
Chello,PL
甲氨蝶呤及其聚谷氨酸衍生物从体外肝细胞的流出。
影响因子：
11.2
作者：
Balinska,M;Galivan,J;Coward,JK
通讯作者：
Coward,JK