THE L5178Y SUBLINES: A SUMMARY OF 40 YEAR STUDIES IN WARSAW

Irena Szumiel


The purpose of this report has been to review and summarise the results of 40 year studies concerning the general characteristics and response to UVC radiation, hydrogen peroxide and ionising radiation of the pair of L5178Y (LY) sublines, LY-R and LY-S, that differ in sen-sitivity to various DNA damaging agents.
Comparison of karyotypes shows a number of differences in the banding patterns. Differences are found in ion transport and the ganglioside pattern of the plasma membranes, as well as in the content and turnover rate of poly(ADP-ribose) polymers. Nuclear matrix proteins show a differential affinity to these polymers. A unique property of the pair of LY sublines is inverse cross-sensitivity to X-rays and hydrogen peroxide, with cross-sensitivities to hydrogen peroxide and UVC, as well as to UVC and a platinum complex (cisplatin analogue). Initial DNA damage and repair and various aspects of the cellular response were determined in cells damaged with these agents. The higher sensitivity of LY-R cells to hydrogen peroxide, as compared to LY-S cells, is causally related to the higher content of iron ions in these cells and less efficient antioxidant defence system. Sensitivity of LY-R cells to UVC radiation and platinum complexes is explained by impaired excision repair (the incision step is missing). The reviewed data on the response of LY sublines to ionising radiation point to 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 the defect (in non-homologous end - joining – NHEJ) explains most features of the cellular response to irradiation, as compared to the repair-competent LY-R cells. The most prominent are: 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 lays 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 by apoptosis, whereas LY-R cells – by necrosis. This observation is consistent with differential expression of proteins that are pro- or antiapoptotic. The prominent role of poly(ADP-ribosylation) in the response of LY-S cells apparently is connected with damage fixation, but is in contrast with other hypersensitive to X/g-radiation cell lines with DSB repair defects. Comparison of LY sublines also indicates that their antioxidant defence system is of considerable importance in their susceptibility to hydrogen peroxide, but much less so in radiosensitivity.

(in Polish)