Thermal Radiosensitization in Heat- and Radiation-sensitive Mutants of CHO Cells

Abstract

Recently, it has been hypothesized (Iliakis and Seaner 1990) that DNA double-strand break (dsb) repair proficiency is a prerequisite for heat radiosensitization on the basis of the finding that the radiosensitive and dsb-repair-deficient mutant xrs-5 cell line shows no significant heat-induced radio-sensitization (not even for severe heat doses), whereas their wildtype counterpart (CHO) did show such an effect. In the current study, the extent of hyperthermic radiosensitization in a new γ-radiation-sensitive cell line, irs-20, recently isolated by Stackhouse and Bedford (1991) and a heat-sensitive mutant hs-36 (Harvey and Bedford 1988) was compared with the radiosensitization of their mutual parent CHO 10B12 cell line. The irs-20 and CHO 10B12 cells have comparable heat (43·5°C) sensitivities, whereas hs-36 and CHO 10B12 show a similar sensitivity to γ- and X-rays. Radiosensitization due to pre-exposure to 43·5°C heating of plateau phase cultures was found for all three cell lines, even after relatively mild heat treatment killing < 20% of cells. Experiments using CHEF electrophoresis confirmed the dsb repair deficiency of the irs-20 cells (Stackhouse and Bedford 1992) and showed that heat inhibited dsb repair in all three cells lines. These data indicate that DNA repair deficiency (overall dsb repair) per se does not imply an absence of the ability for heat radiosensitization.