Modification of radiation and dihydroxyanthraquinone-induced cell lethality by cysteamine and N-ethylmaleimide.

The effect of alteration of sulfhydryl levels on the cell lethality induced by ionizing radiation and dihydroxyanthraquinone (DHAQ) was investigated in cultured Chinese hamster V79 cells. DHAQ produces a potentiation of radiation-induced cell lethality, both by increasing the slope and decreasing the shoulder of the survival curve. It has been suggested that DHAQ functions through the production of free radicals which then produce DNA strand breaks and crosslinks, resulting in cytotoxicity. If this mode of action predominates, then one would expect to be able to change the degree of cell kill by modifying conditions such that free radical processes were altered. This was accomplished by the addition of N-ethylmaleimide (NEM) or Cysteamine (CYS) to the culture medium during treatment with DHAQ. It was observed that the combination of DHAQ and NEM did not produce more cytotoxicity than would be expected from an additive interaction. Likewise, CYS did not reduce the cytotoxicity induced by DHAQ. When cells were treated with DHAQ and radiation plus either NEM or CYS, the resultant survival was consistent with an additive interaction between the potentiation of DHAQ for radiation-induced cell kill and the extra effect of NEM or CYS. These results indicate that alterations of sulfhydryl levels do not produce changes in the cytotoxicity induced by DHAQ, nor in the enhancement by DHAQ of radiation-induced lethality. More investigation is required before definite conclusions can be reached as to the mechanisms of action by which DHAQ, alone or in combination with ionizing radiation, induces mammalian cell lethality.