The number of platinum atoms binding to DNA, RNA and protein molecules of HeLa cells treated with cisplatin at its mean lethal concentration.
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.
Akaboshi
M
M
Research Reactor Institute, Kyoto University, Osaka.
Kawai
K
K
Maki
H
H
Akuta
K
K
Ujeno
Y
Y
Miyahara
T
T
D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D004273:DNA, Neoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D007928:Lethal Dose 50; D009363:Neoplasm Proteins / Q000378:metabolism*; D010984:Platinum / Q000378:metabolism* / Q000493:pharmacokinetics; D012334:RNA, Neoplasm / Q000378:metabolism*; D011868:Radioisotopes; D013347:Subcellular Fractions / Q000378:metabolism
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011868:Radioisotopes; D010984:Platinum; D002945:Cisplatin