Differential DNA double strand break fixation dependence on poly(ADP-ribosylation) in L5178Y and CHO cells.
OBJECTIVE
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.


METHODS
Cells (asynchronous, logarithmic phase) were pre-incubated with 2 mM aminobenzamide at 37 or 25 degrees C, X-irradiated with 10 Gy and allowed to repair DNA breaks for 15, 60 and 120 min at 37 or 25 degrees C. The remaining double-strand break were estimated by the neutral comet assay.


RESULTS
At 37 degrees 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 degrees 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.


CONCLUSIONS
The reported results indicate that poly(ADP-ribosylation) can be an important modulator of the conversion of DNA damage to lethal events.
Wojewódzka
M
M
Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Dorodna 16, PL-03-195 Warsaw, Poland.
Kruszewski
M
M
Sochanowicz
B
B
Szumiel
I
I
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005260:Female; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013696:Temperature
D001549:Benzamides; D004268:DNA-Binding Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases