Abstract
Abstract Background: Fanconi Anemia is an autosomal recessive disorder marked by a dysfunction of DNA repair, an increased sensitivity to DNA crosslinking agents, and some patients poorly tolerating ionizing irradiation. We determined the radiosensitivity of two Fanconi patient cell lines and we determined if the nitroxide radioprotector Tempo or a novel mitochondrial targeted nitroxide JP4-039 could alter their radiosensitivity. Materials and Methods: Fanconi patient derived fibroblastic cell lines, PD326 and PD20F, and their respective transgene restored cell lines FancG and FancD2 were irradiated to doses ranging from 0 to 8 Gy in the presence or absence of Tempo or JP4-039 (10 µm), plated, and colonies greater than 50 cells were counted eight days later. Results: The PD20F cell line was more radiosensitive compared to the restored FancD2 cell line (n = 1.6 + 0.2 and 10.7 + 3.1, respectively, p = 0.0423). In contrast the PD326 cell line was more radioresistant than its restored FancG cell line as seen by an increased shoulder on the survival curve (n = 8.1 + 1.4 and 2.2 + 0.3, respectively, p = 0.0174). JP4-039 but not Tempo increased radioresistance in the PD326 (n = 15.7 + 2.5, p = 0.0373), and FancG cell lines (10.2 + 2.1, p = 0.0151). Conclusions: The human Fanconi Anemia cell line PD326 is radioresistant when compared to its transgene restored FancG cell line, and this radioresistance is increased by treatment with the mitochondrial targeted nitroxide JP4-039. In contrast, PD20F is more radiosensitive when compared to its transgene restored FancD2 cell line. Testing the efficacy of JP4-039 and Tempo on mitigating the effects of mitomycin C treatment is being evaluated. Supported by 2U19A1068021-06 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2503. doi:10.1158/1538-7445.AM2011-2503
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