This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Krishnaswamy, G. Articles by Dewey, W. C. Search for Related Content PubMed PubMed Citation Articles by Krishnaswamy, G. Articles by Dewey, W. C.

Cell Killing and Chromosomal Aberrations Induced in Chinese Hamster Ovary Cells by Treating with Cisplatin at 41.5°C during G₁ or Late S Phase¹

Radiation Oncology Research Laboratory, University of California, San Francisco, California 94143

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°C with cisplatin (0.25–1.25 µg/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°C could be reduced 4–6-fold compared with treatment at 37°C. For low cisplatin concentrations of less than 0.5–0.7 µg/ml (survival, 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 µg/ml, cisplatin cytotoxicity predominated, and for both cell killing and chromosomal aberrations, the cells treated in G₁ were 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°C or 41.5°C in either G₁ or late S. These results suggest that cisplatin administered at 37°C or 41.5°C causes cell lethality primarily by the induction of chromosomal aberrations.

¹ Supported by NCI Grants CA31813 and CA02915.

² To whom requests for reprints should be addressed, at Radiation Oncology Research Laboratory, MCB 200, P.O. Box 0806, University of California, San Francisco, CA 94143.

Received 9/ 3/92. Accepted 1/11/93.