Relationship between Cell-killing Efficiency and Number of Platinum Atoms Binding to DNA, RNA, and Protein Molecules in HeLa Cells Treated withcis-Diamine(glycolato)platinum(II)

Autor: Mitsuhiko Akaboshi, Kenichi Kawai, Koji Ono, Yuko Kinashi, Shin-ichiro Masunaga
Rok vydání: 1996
Předmět:
Zdroj: Japanese Journal of Cancer Research : Gann
ISSN: 0910-5050
DOI: 10.1111/j.1349-7006.1996.tb03156.x
Popis: HeLa S-3 cells were treated with 195m Pt-radiolabeled cis-diamine(glycolato)platinum(II) (254-S) under various conditions, and the relationship between the lethal effect and the numbers of Pt atoms binding to DNA, RNA, and proteins was examined. The mean lethal concentrations for the cells treated with 254-S at 37 degrees C for 0.5, 1, 2, and 3 h were 67.1, 47.0, 26.8 and 8.1 microM, respectively. Using identically treated cells, we determined the numbers of Pt atoms combined with DNA, RNA, and protein molecules after fractionation of the cells. In this way, the D 0 values (D 0, the dose that causes an average of one lethal event per member of the population), expressed as the drug concentration, could be related to the number of Pt atoms combined with each fraction. The efficiency of the Pt atom in killing the cells, expressed as the reciprocal of the D 0 values, was then calculated for each fraction. The results suggested that DNA was the primary target for cell killing by 254-S. The target volumes for DNA were 3.96, 4.97, and 11.77 x 10(4) nucleotides for 1-, 2-, and 3-h treated cells, respectively. In terms of the target volume, the cell-killing effects of 254-S were comparable to those of cis-diamine-dichloroplatinum(II) (CDDP), for which the target volumes under identical conditions were determined to be 5.17, 5.71, and 10.3x10 4 nucleotides, respectively, while in terms of the mean lethal dose (D 0), the cell-killing effects of 254-S were lower than those of CDDP by a factor of 5.1 (47.0/9.3), 4.0 (26.8/6.7), or 2.5 (8.1/3.2) for 1-, 2-, or 3-h treatment, respectively.
Databáze: OpenAIRE