Differential DNA double strand break fixation dependence on poly(ADP-ribosylation) in L5178Y and CHO cells
Authors: M. Wojewódzka; M. Kruszewski; B. Sochanowicz; I. Szumiel
Source: International Journal of Radiation Biology, Volume 80, Number 7, July 2004 , pp. 473-482(10)
Publisher: Informa Healthcare
Abstract:Purpose: To investigate the role of poly(ADP-ribosylation) in DNA double-strand break repair and fixation in murine lymphoma L5178Y (LY) sublines, LY-R and LY-S, and a pair of Chinese hamster ovary lines: wild-type and mutant xrs6 cells, that have differences in repair competence and degree of radiosensitization with poly(ADP-ribosylation) inhibitors.Materials and methods: Cells (asynchronous, logarithmic phase) were pre-incubated with 2 mM aminobenzamide at 37 or 25°C, X-irradiated with 10 Gy and allowed to repair DNA breaks for 15, 60 and 120 min at 37 or 25°C. The remaining double-strand break were estimated by the neutral comet assay.Results: At 37°C, no effect of AB treatment on the repair kinetics was observed either in xrs6 or Chinese hamster ovary (wild-type) cells. In contrast, aminobenzamide decreased the repair of double-strand break in the LY-S line but not the LY-R line, in agreement with the previously observed radiosensitization of LY cells by poly(ADP-ribosylation) inhibition. However, double-strand break rejoining in the repair competent cell lines, Chinese hamster ovary and LY-R, also was affected by aminobenzamide when the post-irradiation incubation was carried out at 25°C. Analysis of these results together with earlier data on LY-S cells have been interpreted in terms of Radford's model of radiation damage fixation.Conclusion: The reported results indicate that poly(ADP-ribosylation) can be an important modulator of the conversion of DNA damage to lethal events.
Document Type: Research article
Publication date: 2004-07-01