Cisplatin induced cell killing and chromosomal aberrations in CHO cells: treated during G1 or S phase

Variation in sensitivity to cisplatin during the cell cycle was studied synchronous cells treated during G₁ or late S phase. The cells were assayed for cell killing, cell-cycle delay, and chromosomal aberrations after they were treated with cisplatin (1–12 μg/ml) for 1 h at 37°C. They were either plated for colony survival, or colcemid was added from 12 to 40 h after plating followed by fixation 4 h later for analysis of chromosal aberrations after the cells completed 1 or 2 cycles (i.e. first or second mitosis). Cells treated with 6 μg/ml exhibited about a 10-h delay during the first cycle after treatment during G₁ compared with about 3 h during the first cycle and 6 h during the second cycle after treatment during late S. In both cases, cells entering metaphase exhibited predominantly chromatid-type breaks and exchanges. For both cell killing and chromosomal aberrations, the cells in G₁ were 1.5–1.6 times more sensitive than those treated in late S, with 1 aberration per cell corresponding to about 37% survival. However, the exchanges and breaks were observed primarily in the first mitosis when cells were treated in G₁ compared with the second mitosis when cells were treated in late S. These results suggest that DNA replication opposite cisplatin cross-links in the DNA results in lethal chromosomal aberrations.