No abstract

This paper examined heat-induced radiosensitization in two Chinese hamster heat-resistant cell lines, HR-1 and OC-14, that were isolated from the same wild-type HA-1 cell line. It found a reduction of the magnitude of heat-induced radiosensitization after exposure to 43 degrees C in both HR-1 and OC-14 cells and a similar reduction after exposure to 45 degrees C in HR-1 cells, but not in OC-14 cells. The effect of heat exposure on a class of ionizing radiation-induced DNA damage that inhibits the ability of nuclear DNA to undergo super-coiling changes was also studied using the fluorescent halo assay in these three cell lines. Wild type cells exposed to either 43 or 45 degrees C before irradiation had a DNA rewinding ability that was intermediate between control and unheated cells, a phenomenon previously described as a masking effect. This masking effect was significantly reduced in HR-1 cells exposed to either 43 or 45 degrees C or in OC-14 cells exposed to 43 degrees C under conditions that heat-induced radiosensitization was reduced. In contrast, the masking effect was not altered in OC-14 cells exposed to 45 degrees C, conditions under which heat-induced radiosensitization was similar to that observed in wild-type HA-1 cells. These results suggest that a reduction in the masking effect is associated with a reduction of the magnitude of heat-induced radiosensitization in the HR-1 and OC-14 heat-resistant cell lines. The reduction of the masking effect in the cell lines resistant to heat-induced radiosensitization was associated with neither a reduction in the magnitude of the heat-induced increase in total nuclear protein content nor major differences in the protein profiles of the nucleoids isolated from heated cells.

Recently, it has been demonstrated that two different thermal resistant states found in Chinese hamster cells, one transient, associated with thermotolerance, and the other permanent, associated with the increased expression of the cognate member of the hsp 70 family, are characterized by faster recovery from heat-induced perturbations in several cellular processes (Laszlo 1992b). These processes include total cellular protein and RNA synthesis, the localization of hsp70, the organization of vimentin, and the protein composition of the nucleus. In the present study, the recovery from heat-induced perturbations in cellular physiology was extended further to two more types of Chinese hamster cells: permanently heat resistant cells in which thermoresistance is associated with the overexpression of hsp27 and heat-sensitive cell lines. When the heat-resistant hsp27 transfected cell lines were compared with the control wild-type cell line, the recovery of protein synthesis from heat-induced inhibition was similar in the normal and hsp27 transfected cells, while the recovery from heat-induced inhibition of total RNA synthesis and the recovery from heat-induced increased association of hsp70 with nuclei were both more rapid in the hsp27 transfected cell lines. In the permanently heat-sensitive cell lines, the kinetics of recovery from heat-induced inhibition of protein synthesis did not correlate with the heat sensitive state. However, delays in the recovery from heat-induced alterations in total cellular RNA synthesis and from heat-induced excess nuclear association of hsp70 were associated with the heat-sensitive state. Overall, these results suggest that the kinetics of recovery from heat-induced alterations in total cellular RNA synthesis and the localization of hsp 70 are putative candidates for being determinants of the cellular response to hyperthermia, and thus have the potential to form the basis of predictive assays for use in conjunction with clinical hyperthermia.