Association of the radiosensitivity of mouse lymphoma strain L5178Y-S with its response to other cytotoxic agents

Mouse lymphoma strain L5178Y-S (LY-S) has been found to be more sensitive than parental strain LY-R to the cytotoxic effects of ionizing radiation, alkylating agents, and compounds which induce topoisomerase II-associated DNA cleavage. In contrast, strain LY-S is more resistant to UV radiation and peroxides than strain LY-R. The authors used the selective pressure of low dose-rate ionizing radiation (0.02 Gy/hr) to obtain two independent phenotypic revertants of strain LY-S which are resistant to ionizing radiation. Although the revertants showed increased resistance to both low dose-rate and high dose-rate ionizing radiation, their response to the cytotoxic effects of alkylating agents, UV radiation, and peroxides remained similar to that of strain LY-S. In contrast, the revertants showed increased resistance to the topoisomerase II inhibitors, m-AMSA and ellipticine. The possibility that an alteration in the interaction between toposiomerase II and DNA in strain LY-S is responsible for its sensitivity to ionizing radiation will be investigated