Effects of Heat Treatment on Radiation Sensitivity: Dictyostelium discoideum

Exposure of mammalian cells to hyperthermic temperature results in both cytotoxicity and radiosensitization; the molecular mechanisms are still obscure. We have investigated the effect of hyperthermia on DNA repair after exposure of UV irradiation which produces simple DNA damage, namely pyrimidine dimers, as compared with ionizing radiation which induces various DNA lesions. We have utilized Dictyostelium discoideum which is a lower eukaryote for which several DNA repair-deficient mutants are available. Though the optimum temperature for cell growth of the amoebae was 23°C, the critical temperature for effective enhancement of cell killng was ca. 30°C. In a wild-type strain (NC4), an increased temperature immediately after UV irradiation resulted in an increase in cell killing, since heat treatment did not inhibit the nicking of DNA strand, but did inhibit removal of pyrimidine dimers and the rejoining of the strand breaks. On the other hand, a radiationsensitive mutant (TW8) defective in an incision step of excision repair did not show an increase in cell killing in response to heat treatment administered after UV irradiation. Similar effects on NC4 as UV irradiation were observed in the case of heat treatment after treatment with 4-nitroquinoline 1-oxide, cis-platinum (II) diamminedichloride or 8-methoxypsoralen photo-addition, which produces excision repairable DNA lesions, not but N-methyl-N'-nitro-N-nitrosoguanidine or methylmethanesulphonate, which produces methylated DNA lesions independent of excision repair. Therefore, it is suggested that the sensitization of heat treatment might be dependent on the depression of excision repair mechanism.