Caffeine and D2O medium interact in affecting the expression of radiation-induced potentially lethal damage

Earlier work (Ben-Hur et al. 1980) has been extended to compare the killing of log-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D2O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D2O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D2O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D2O medium is similar. For example, the kinetics of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D2O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. That is, exposures to caffeine, which by themselves did not enhance killing (up to 1 mM for 2 h), decreased the enhanced killing due to D2O medium, Reciprocally, D2O medium reduced the enhanced killing due to high concentrations of caffeine (greater than 1 mM). Thus, although caffeine and D2O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect.