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.