The repair of double-strand DNA breaks correlates with radiosensitivity of L5178Y-S and L5178Y-R cells.
To better understand the basis for the difference in radiosensitivity between the variant murine leukemic lymphoblast cell lines L5178Y-R (resistant) and L5178Y-S (sensitive), the production and repair of DNA damage after X irradiation were measured by the DNA alkaline and neutral elution techniques. The initial yield of single-strand DNA breaks and the rates of their repair were found to be the same in both cell lines by the DNA alkaline elution technique. Using the technique of neutral DNA elution, L5178Y-S cells exhibited slightly increased double-strand breakage immediately after irradiation, most significantly at lower doses (i.e., less than 10 Gy). Nevertheless, even at doses that yielded equal initial double-strand breakage of both cell lines, the survival of L5178Y-S cells was significantly less than that of L5178Y-R cells. When the technique of neutral DNA elution was employed to measure the kinetics of DNA double-strand break repair, both cell lines exhibited biphasic fast and slow components of repair. However, the double-strand repair rate was much lower in the radiosensitive L5178Y-S cells than in the L5178Y-R cells (T1/2 of 60 vs 16 min). This difference was more pronounced in the fast-repair component. These results suggest that the repair of double-strand DNA breaks is an important factor determining the radiosensitivity of L5178Y cells.
Wlodek
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Department of Medical Oncology, University of Texas M. D. Anderson Hospital and Tumor Institute, Houston 77030.
Hittelman
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D000818:Animals; D004247:DNA / Q000528:radiation effects; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects*; D007940:Leukemia L5178 / Q000235:genetics* / Q000473:pathology; D007942:Leukemia, Experimental / Q000235:genetics*; D051379:Mice; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D004273:DNA, Neoplasm; D004247:DNA