Platinum incorporation and differential effects of cis- and trans-diamminedichloroplatinum(II) on the growth of mouse leukemia P388/D1.
The parallel effects of cis-diamminedichloroplatinum(II) (1 microM) or trans-diamminedichloroplatinum(II) (20 microM) on the growth of mouse leukemia P388/D1 in culture, on the cellular content of protein/DNA, on the average cell volume, and on the distribution in different phases of the cell cycle were measured over a period of 70 h and compared with the amount of platinum residing in the cells. Despite different concentrations in the culture medium, similar amounts of cis- and trans-diamminedichloroplatinum(II) were incorporated. The platinum content of cells passed through an early concentration maximum in the millimolar range and decreased during prolonged times of incubation. Effects of cis-diamminedichloroplatinum(II) were marked and irreversible whereas those of trans-diamminedichloroplatinum(II) were small and transient. Proliferation was inhibited, while synthesis of protein and DNA continued almost unaffected. Cells were arrested in G2-phase of the cell cycle, and their volume increased correspondingly. The results suggested an inhibition of mitotic events, rather than of DNA replication, that caused cell arrest.
Just
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Institut für Biophysik und physikalische Biochemie, Universität Regensburg, Federal Republic of Germany.
Holler
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D007941:Leukemia P388 / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis; D010984:Platinum / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C034697:transplatin; D010984:Platinum; D002945:Cisplatin