Akaboshi M, Kawai K, Maki H, Akuta K, Ujeno Y, Miyahara T
Research Reactor Institute, Kyoto University, Osaka.
Jpn J Cancer Res. 1992 May;83(5):522-6. doi: 10.1111/j.1349-7006.1992.tb01959.x.
HeLa S-3 cells were treated with 195mPt-radiolabeled cis-diamminedichloroplatinum(II) (CDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with CDDP at 37 degrees C for 1, 2 and 3 h were 2.8, 2.0 and 1.1 microgram/ml, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes expressed as the reciprocals of D0 values were calculated for each fraction. The results provide strong support for the idea that DNA is the primary target for cell killing by CDDP, and the target volumes were 5.17 x 10(4), 5.71 x 10(4) and 1.03 x 10(5) nucleotides for 1, 2 and 3 h treated cells, respectively.
在不同条件下，用195mPt放射性标记的顺二氯二氨铂（II）（CDDP）处理HeLa S - 3细胞，并研究致死效应与结合到DNA、RNA和蛋白质上的铂原子数量之间的关系。在37℃下用CDDP处理细胞1、2和3小时，其平均致死浓度分别为2.8、2.0和1.1微克/毫升。使用经相同处理的细胞，采用施奈德方法对细胞进行分级分离后，测定结合到DNA、RNA和蛋白质分子上的铂原子数量。通过这种方式，将以药物浓度给出的D0值替换为结合到各组分上的铂原子数量，然后计算出各组分以D0值的倒数表示的靶体积。结果有力支持了DNA是CDDP杀伤细胞的主要靶点这一观点，对于处理1、2和3小时的细胞，其靶体积分别为5.17×10⁴、5.71×10⁴和1.03×10⁵个核苷酸。
