Differences in repair of radiation induced damage in two human tumor cell lines as measured by cell survival and alkaline DNA unwinding |
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Authors: | J H Schwach?fer R P Crooijmans H Hoogenhout H B Kal R Q Schaapveld J Wessels |
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Institution: | Department of Radiotherapy, University Hospital, Nijmegen, The Netherlands. |
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Abstract: | We studied the relationship between the repair of radiation induced DNA strand breaks and cellular repair kinetics in two human tumor cell lines, NB-100 (neuroblastoma) and HN-1 (squamous cell carcinoma). Damage was quantified using the fluorometric analysis of DNA unwiding (FADU) for DNA damage, and cell survival was assessed using a clonogenic assay. In plateau phase cells repair of sublethal damage was virtually absent in NB-100 after 4 Gy (recovery ratio 1.0), whereas HN-1 cells did show sublethal damage repair (recovery ratio 1.4). Repair of potentially lethal damage was more pronounced in NB-100 cells (recovery ratio 2.3) than in HN-1 cells (recovery ratio 1.7) after 4 Gy. Graded doses of X-rays induced comparable levels of DNA damage in both tumor cell lines. However, in HN-1 cells more DNA strand breaks were repaired after 4 Gy, leaving about 25% of the initial damage unrepaired, whereas in NB-100 about 50% was unrepaired. This higher fraction of unrepaired DNA damage correlated well with the degree of sublethal damage repair which was lower in NB-100 than in HN-1 cell, but it did not correlate with the repair of potentially lethal damage, which was higher in NB-100 than in HN-1. Since the level of damage remaining post-irradiation may be the critical variable for survival, the FADU technique can contribute in elucidating the relationship between radiosensitivity and DNA damage repair capacity. |
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