Mouse Lymphoma Cells that Undergo Interphase Death Show Markedly Increased Sensitivity to Radiation-induced DNA Double-strand Breakage as Compared with Cells that Undergo Mitotic Death

Abstract

The relationship between radiation-induced DNA double-strand breakage (dsb) and reproductive death (clonogenicity) for two mouse lymphoma cell lines was compared with that for the fibroblast-like hamster cell line V79. One of the lymphoma lines (STRij-4-2.2), which undergoes rapid disintegration following cytotoxic insult, showed extreme sensitivity to gamma-ray or DNA-associated 125I decay-induced DNA dsb (7 +/- 1 125I decays per clonogenic lethal event). Surprisingly, the other lymphoma line (WEHI-22.1), which does not undergo rapid disintegration, was also much more sensitive to DNA dsb than were V79 cells (17 +/- 1 versus 61 +/- 2 125I decays per clonogenic lethal event). Ultrastructure, DNA degradation, and flow cytometric cell cycle data suggested that both lymphoma cell lines may undergo interphase death, but that the induction of this process in WEHI-22.1 may depend upon blockage in the G2 phase. It is concluded that there are marked differences between the radiation responses of lymphoma and fibroblast lines, that there may be different forms of radiation-induced interphase death, and that the low number of DNA dsb required to produce a clonogenic lethal event in cells undergoing interphase death could explain the radiosensitivity of organs such as ovary, testis and thymus.