Telomere length in lymphoblast cell lines derived from clinically radiosensitive cancer patients.

Approximately 1-5 percent of cancer patients suffer from significant side effects in normal tissue after radiotherapy (RT). Although RT is an effective cancer therapy, treatment dose intensities are restricted to minimize the incidence of such normal tissue reactions. Therefore, most patients receive lower dose intensities than can be tolerated in normal tissue. A primary aim for radiation oncology is to identify radiosensitive (RS) individuals prior to treatment. Such predictive ability should result in an improvement in tumor control rates and/or a reduction in the incidence of RT side effects. Recent evidence suggests a link between RS and telomere length. A positive correlation between cellular RS and telomere length in a cohort of breast cancer patients has been reported. Furthermore,individuals with cancer-prone recessive RS syndromes, such as ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome(NBS), have shortened telomeres. To determine whether the association between telomere length and RS could be used as a predictive assay to prospectively identify RS cancer patients, we utilized a bank of lymphoblastoid cell lines (LCLs) derived from 33 RS patients, along with 18 LCL samples from RT patients who did not have severe reactions, to assess the link between RS and telomere length. We found a subset of RS patient LCLs had abnormally long telomere lengths, so these data suggest that RS could potentially be predicted for a subset of RS patients based on telomere length in LCLs, and contribute to therapy individualization.

Uncoupling of telomere length and radiosensitivity in mouse lymphoma cell lines of similar genetic background.

PURPOSE: To investigate the link between radiosensitivity and telomere length in murine lymphoid cell line stocks that have similar genetic backgrounds but different radiosensitivities. MATERIALS AND METHODS: We used two stocks from both the parental L5,178Y-R cell line and the repair-deficient radiosensitive subline, L5,178Y-S, to assess telomere length. We used terminal restriction fragment analysis and flow-fluorescence in situ hybridization (FISH) telomere length assessment to determine telomere lengths in the related radiosensitive and non-radiosensitive cell lines. Each cell line was further tested for retention of its original radiation response phenotype using cell growth assays after treatment with ionizing radiation. RESULTS: One stock of L5,178Y-R cells had long telomeres, whereas the other stock had short telomeres. Likewise, one stock of L5,178Y-S cells had long telomeres, whereas the other stock had short telomeres. Telomere lengths in these cell lines were relatively stable for over 80 divisions in culture. Each cell line was confirmed to have retained its original radiosensitivity phenotype. CONCLUSION: We conclude that radiosensitivity is independent of telomere length in these genetically similar cell lines.