The effects of 9-beta-D-arabinofuranosyladenine on the repair of DNA strand breaks in X-irradiated Ehrlich ascites tumour cells
Bryant, P.E.; Blöcher, D.
International Journal of Radiation Biology and Related Studies in Physics Chemistry and Medicine 42(4): 385-394
1982
ISSN/ISBN: 0020-7616 PMID: 6983507 Document Number: 195328
The effects of the DNA synthesis inhibitor 9-.beta.-D-arabinofuranosyladenine (.beta.-ara A), a nucleoside analog of desoxyadenine, on repair of DNA single and double strand breaks (ssb and dsb) were investigated in X-irradiated Ehrlich ascites tumor cells. Repair of ssb was followed using the unwinding method, and repair of dsb was measured with both the unwinding and the neutral sucrose centrifugation methods. Repair of ssb was inhibited in the presence of .beta.-ara A; however, even at high concentrations some repair took place. Apparently, this proportion of the breaks (about 30%) is joined by polynucleotide ligase, and do not require insertion of nucleotides. Dsb repair was strongly inhibited by .beta.-ara A, the inhibition being complete at high concentrations. Possibly, dsb repair has an absolute requirement for DNA polymerization. When cells were treated with .beta.-ara A (200 .mu.mol/l, 2 h) after irradiation, dsb repair was inhibited; however, when the drug was washed away, repair of dsb returned. At 6 h more breaks persisted in .beta.-ara A treated cells than in the untreated controls. Cells treated after X-irradiation with .beta.-ara A for 7 h at 120 .mu.mol/l in conditioned medium, and afterwards in fresh medium free of .beta.-ara A for 24 h, showed a higher number of residual dsb than control cells. These residual dsb may be relevant to the increased killing effect caused by adding .beta.-ara A to X-irradiated cultures.