The Enhancement of Cell Lethality and Changes in Production and Repair of DNA Damage by Hypertonic Treatment after Exposure to X Rays, Belomycin, and Neocarzinostatin

Abstract

Chinese hamster ovary cells were treated with hypertonic 0.5 M NaCl solution after exposure to X rays or the radiomimetic drugs bleomycin or neocarzinostatin. The cytotoxicity of these agents was greatly enhanced by the hypertonic treatment. On the other hand, no effect was observed after exposure to ultraviolet light, and a significant effect was obtained with mitomycin C (MMC), adriamycin (ADR), and ethyl methanesulfonate (EMS). Assays by filter elution revealed that hypertonicity had various effects on the damage produced by the different agents. Strand breaks resulting from exposure to X rays and radiomimetic agents were sensitive to hypertonic treatment. Hypertonicity caused the production of new lesions and inhibited the rejoining of DNA strand breaks, both of which may be responsible for the enhanced cytotoxicity. On the other hand, the formation of crosslinks by MMC or protein-associated double-strand breaks by ADR, the major forms of damage by which these agents cause cytotoxicity, was not affected by hypertonic treatment. As strand breaks are known to be produced by MMC or ADR, they could account at least partly for the sensitization. However, various kinds of damage are produced by MMC, and any of these could be involved in the sensitization. To our knowledge EMS produces only base damage. Thus hypertonic treatment may have an effect on various types of damage.