Cell killing and chromosomal aberrations induced in Chinese hamster ovary cells by treating with cisplatin at 41.5 degrees C during the G1 or late S phase.
Variation in sensitivity to cisplatin during the cell cycle was studied in synchronous Chinese hamster ovary cells treated during G1 or late S for 1 h at 41.5 degrees C with cisplatin (0.25-1.25 micrograms/ml, 0.8-4.2 x 10(-6) M). The cells were assayed for cell killing and chromosomal aberrations. Either they were plated for colony survival, or colcemid was added from 12 to 40 h after plating followed by fixation 4 h later for analysis of chromosomal aberrations after the cells completed 1 or 2 cycles (i.e., first or second mitosis). When the cells were treated either in G1 or late S, the cells entering metaphase exhibited primarily chromatid-type deletions and exchanges. However, aberrations were observed primarily in the first mitosis when cells were treated in G1 compared with aberrations being observed in both the first and second mitoses when cells were treated in late S. For a given amount of cytotoxicity or cytological damage, the cisplatin concentration at 41.5 degrees C could be reduced 4-6-fold compared with treatment at 37 degrees C. For low cisplatin concentrations of less than 0.5-0.7 microgram/ml (survival, approximately 0.3), heat killing predominated, and cells treated in S phase were more sensitive than those treated in G1. However, for cisplatin concentrations greater than 0.5-0.7 microgram/ml, cisplatin cytotoxicity predominated, and for both cell killing and chromosomal aberrations, the cells treated in G1 were approximately 1.5 times more sensitive than those treated in late S. Furthermore, the positive correlation between survival and aberration frequency was similar for cells treated at 37 degrees C or 41.5 degrees C in either G1 or late S. These results suggest that cisplatin administered at 37 degrees C or 41.5 degrees C causes cell lethality primarily by the induction of chromosomal aberrations.
Krishnaswamy
G
G
Radiation Oncology Research Laboratory, University of California, San Francisco 94143.
Dewey
W C
WC
D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D016193:G1 Phase; D006358:Hot Temperature; D016196:S Phase
D004247:DNA; D002945:Cisplatin