Heat-induced Lethality and Chromosomal Damage in Synchronized Chinese Hamster Cells Treated with 5-bromodeoxyuridine

Summary

Synchronous Chinese hamster cells exposed to heat treatments of 45·5°c were very sensitive during S phase when chromosomal damage could account for cell killing, i.e. as for x-irradiated cells, the 37 per cent survival value for heated cells was observed when there was about one aberration per cell. However, the aberration frequency was very low and could not account for cell killing when the cells were heated, either during mitosis when they were most sensitive in terms of lethality, or during G₁ when they were most resistant. Furthermore, about 50 per cent of the deletions in these cells heated in mitosis or G, occurred at the secondary constriction of the X chromosome. Incorporation of BUdR into DNA prior to synchronizing the cells had only an additive interaction with heat administered during G₁ or S. This interaction was characterized by a reduction in the shoulder of the dose-response curves observed for both chromosomal aberrations and cell killing.

These findings contrast greatly with those for x-irradiation in that, (1) the S phase is the most resistant phase to x-irradiation, (2) there is a positive correlation between x-ray induced chromosomal aberrations and cell killing throughout the cycle, and (3) incorporation of BUdR into DNA has a synergistic interaction with x-rays, characterized by a two-fold reduction in the dose required for a given amount of damage. From these experiments, as they relate to findings in the literature, the hypothesis is presented that heat inactivation of mammalian cells results from the denaturation of proteins associated with the DNA. In mitotic cells, however, denaturation of spindle protein appears to be most critical.