THERMAL RADIOSENSITIZATION IN HEAT-SENSITIVE AND RADIATION-SENSITIVE MUTANTS OF CHO CELLS

Recently, it has been hypothesized (Iliakis and Seaner 1990) that DNA double-strand break (dsb) repair proficiency is a prerequisite for hea t radiosensitization on the basis of the finding that the radiosensiti ve and dsb-repair-deficient mutant xrs-5 cell line shows no significan t heat-induced radiosensitization (not even for severe heat doses), wh ereas their wildtype counterpart (CHO) did show such an effect. In the current study, the extent of hyperthermic radiosensitization in a new gamma-radiation-sensitive cell line, irs-20, recently isolated by Sta ckhouse and Bedford (1991) and a heat-sensitive mutant hs-36 (Harvey a nd Bedford 1988) was compared with the radiosensitization of their mut ual parent CHO 10B12 cell line. The irs-20 and CHO 10B12 cells have co mparable heat (43.5-degrees-C) sensitivities, whereas hs-36 and CHO 10 B12 show a similar sensitivity to gamma- and X-rays. Radiosensitizatio n due to pre-exposure to 43-5-degrees-C heating of plateau phase cultu res was found for all three cell lines, even after relatively mild hea t treatment killing < 20% of cells. Experiments using CHEF electrophor esis confirmed the dsb repair deficiency of the irs-20 cells (Stackhou se and Bedford 1992) and - showed that heat inhibited dsb repair in al l three cells lines. These data indicate that DNA repair deficiency (o verall dsb repair) per se does not imply an absence of the ability for heat radiosensitization.