Thermal radiosensitization in two pairs of CHO wild-type and radiation-sensitive mutant cell lines

Abstract

Two pairs of Chinese hamster ovary cell lines, each comprising a parental normal-responding and a radiation-sensitive mutant, were tested for their X-radiation sensitivity, hyperthermia sensitivity and thermal radiosensitization. The relative radiation responses were similar to those already published in the literature, indicating that the mutant cell lines, V-3 and 5-11, were extremely sensitive to radiation while their parental strains (AA8-4 and K1) exhibited normal sensitivity. The hyperthermia response of V3 was the same as that of the parental cell line AA8-4; the thermal sensitivity of 5-11 was greater than that of its parental line K1 but this difference decreased at higher temperatures (greater than 43°C). These data indicate that the hyperthermia response and its targets are probably not related to the mutation-causing radiation sensitivity in the two pairs of parent-mutant cell lines. When heat and radiation were combined, the thermal enhancement of radiation sensitivity for different heat treatments was the same or larger in the mutant than in the parental cell lines. The mutants are known to be deficient in potentially lethal damage repair (PLDR), sublethal damage repair (SLDR) and repair of double-stranded DNA breaks; however, these deficiencies did not impair thermal radiosensitization, indicating that thermal radiosensitization may not be through these pathways in these particular mutants. In addition, the parental cell lines exhibited a significant sequence dependence of thermal radiosensitization (i.e. whether heat was applied before or after irradiation) at low survival levels (10^--⁴); this sequence dependence was very small to absent in the mutant cell lines at these survival levels.

Key Words:

• Radiation-sensitive mutants
• thermal radiosensitization
• hyperthermia