L5178Y sublines: a look back from 40 years. Part 2: response to ionizing radiation

Abstract

The aim was to review and summarize the results of 40 years of study concerning the response to ionizing radiation of the pair of L5178Y (LY) sublines, LY-R and LY-S, that differ in sensitivity to various DNA-damaging agents, among them X- and gamma-rays. The reviewed data indicate the key importance of DNA damage repair and fixation for the ultimate fate of the irradiated LY cell. The cause of slow double-strand break (DSB) repair in LY-S cells is not identified, but a defect in non-homologous end-joining (NHEJ) would explain most features of the cellular response of LY-S cells to irradiation, as compared with repair-competent LY-R cells. The most prominent features are the very high radiosensitivity of G1 cells, extensive poly(ADP-ribose)-dependent damage fixation, long G2 arrest, considerable chromosomal damage seen as premature chromatin condensation (PCC) fragments and aberrations in metaphase cells. The main cause of radiosensitivity difference between LY sublines is in DNA repair/damage fixation ability. At the level of damage corresponding to a comparable lethal effect, the type of death differs between LY sublines; LY-S cells die in considerably greater proportion by apoptosis than LY-R cells, whereas the latter die in greater proportion by necrosis. This observation is consistent with differential expression of proteins that are pro- or anti-apoptotic. The prominent role of poly(ADP-ribosylation) in the response of LY-S cells apparently is connected with damage fixation, but is in contrast to other cell lines hypersensitive to X- or gamma-radiation with DSB repair defects.