Effects of cis-platinum(II) diamminedichloride on survival and the rate of DNA synthesis in synchronously growing Chinese hamster V79-379A cells in the absence and presence of caffeine inhibited post-replication repair; evidence for an inducible repair mechanism
Abstract
The mechanism by which cis-Platinum(II)diamminedichloride, (cis-Pt(II)), inhibited DNA synthesis was investigated using synchronously growing Chinese hamster V79-379A cells. The progression of G1 phase treated cells into S phase was not inhibited. However the rate of DNA synthesis throughout the S phase was depressed in a dose dependent manner compared to a control. The peak rate of DNA synthesis was delayed and the duration of the S phase was extended resulting in a dose dependent delay in the timing of mitosis in the first cell cycle after treatment. The delay in the timing of mitosis after the second S phase in treated cells was comparable to the delay observed after the first cycle. Post treatment incubation of cells in the presence of a non toxic concentration of caffeine resulted in an alteration in the pattern of DNA synthesis, leading to a reversal of the dose dependent delay in the timing of the peak rate of DNA synthesis to a position corresponding to the control. Caffeine potentiated the toxicity of cis-Pt(II) only if it was added during the first cell cycle after treatment. The patterns of DNA synthesis in synchronous cultures of Chinese hamster V79-379A cells after cis-Pt(II) treatment appeared to be similar to tho...Continue Reading