DNA lesions in hyperthermic cell killing: effects of thermotolerance, procaine, and erythritol.
When HeLa S3 cells were subjected to 45 degrees C hyperthermia, DNA lesions were detected by the use of the alkaline unwinding/hydroxylapatite method. The number of lesions formed was not affected when the cells were made thermotolerant by either an acute (15 min 44 degrees C + 5 h 37 degrees C) or a chronic (5 h 42 degrees C) pretreatment before 45 degrees C hyperthermia. The presence of 10 mM procaine (heat sensitizer) or 0.5 M erythritol (heat protector) during hyperthermia also had no effect on the rate of formation of heat-induced alkali labile DNA lesions. These observations do not support a concept where DNA lesions are considered to be the ultimate cause of hyperthermic cell killing. Both drugs, however, influenced the rate of repair of radiation-induced strand breaks when present during preirradiation heat treatment. We conclude that the initial number of heat-induced alkali labile DNA lesions is not directly related to cell survival. It cannot be excluded, however, that differences in posthyperthermic repair of these lesions may lead to a positive correlation between residual DNA damage and survival after the different experimental conditions.
D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004896:Erythritol / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects / Q000528:radiation effects; D006358:Hot Temperature; D006801:Humans; D011343:Procaine / Q000494:pharmacology*; D014965:X-Rays
D011343:Procaine; D004247:DNA; D004896:Erythritol