J P Banáth1, M Fushiki, P L Olive. 1. Medical Biophysics Department, British Columbia Cancer Research Centre, Vancouver, Canada.
Abstract
PURPOSE: To characterize inter- and intra-individual differences in X-ray-induced DNA strand break rejoining kinetics in human peripheral white blood cells (WBC) obtained from 10 healthy volunteers. MATERIALS AND METHODS: The alkaline and neutral versions of the comet assay were used to measure the rate of rejoining of predominantly single-strand breaks (ssb) following exposure to 8 Gy and double-strand breaks (dsb) following 75 Gy. RESULTS: All cells within a population responded in a similar fashion to induction of ssb and dsb; however, a subset of the WBC appeared to rejoin ssb more rapidly. For the 10 individuals examined, the percentage of ssb rejoined by the rapid component(s) was 47 +/- 16% and the rejoining half-time for the slow component was 1.3 +/- 0.4 h. By 24 h after 8 Gy, 4.9 +/- 3.8% of the initial ssb remained. For dsb rejoining, 58 +/- 11% of the initial damage was still present 4h after 75 Gy and by 24 h 32% of the initial level of damage was still detected. Heavily damaged cells present 24 h after 75 Gy varied from 4% to 50% and were excluded from the analysis of repair rates. CONCLUSIONS: Inter-individual variability exceeded intra-individual variability for 2 of 4 endpoints examined for ssb repair, but not for dsb repair. It was concluded that DNA damage measured using the comet assay could identify a range in the X-ray repair responses of WBC from different normal individuals. Whether these differences correlate with differences in cell killing by radiation remains to be determined.
PURPOSE: To characterize inter- and intra-individual differences in X-ray-induced DNA strand break rejoining kinetics in human peripheral white blood cells (WBC) obtained from 10 healthy volunteers. MATERIALS AND METHODS: The alkaline and neutral versions of the comet assay were used to measure the rate of rejoining of predominantly single-strand breaks (ssb) following exposure to 8 Gy and double-strand breaks (dsb) following 75 Gy. RESULTS: All cells within a population responded in a similar fashion to induction of ssb and dsb; however, a subset of the WBC appeared to rejoin ssb more rapidly. For the 10 individuals examined, the percentage of ssb rejoined by the rapid component(s) was 47 +/- 16% and the rejoining half-time for the slow component was 1.3 +/- 0.4 h. By 24 h after 8 Gy, 4.9 +/- 3.8% of the initial ssb remained. For dsb rejoining, 58 +/- 11% of the initial damage was still present 4h after 75 Gy and by 24 h 32% of the initial level of damage was still detected. Heavily damaged cells present 24 h after 75 Gy varied from 4% to 50% and were excluded from the analysis of repair rates. CONCLUSIONS: Inter-individual variability exceeded intra-individual variability for 2 of 4 endpoints examined for ssb repair, but not for dsb repair. It was concluded that DNA damage measured using the comet assay could identify a range in the X-ray repair responses of WBC from different normal individuals. Whether these differences correlate with differences in cell killing by radiation remains to be determined.
Authors: Andrzej R Trzeciak; Janice Barnes; Ngozi Ejiogu; Kamala Foster; Larry J Brant; Alan B Zonderman; Michele K Evans Journal: Free Radic Biol Med Date: 2008-09-17 Impact factor: 7.376