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|Title:||Enhancement of radiation induced cell death in chicken B lymphocytes by withaferin A|
|Authors:||Devi, P Uma|
|Abstract:||Withaferin A (WA), a plant withanolide, has shown significant radiosensitizing effect <i style="">in vitro</i> and <i style="">in vivo</i>. Inhibition of DNA repair has been suggested as a mechanism of radiosensitization by WA. To test this, the effect of withaferin A on survival of DT40 chicken B-lymphocyte cell line and its repair deficient single gene mutants Rad54<sup>-/-</sup>, Ku70<sup>-/-</sup> and double mutant Ku70<sup>-/- </sup>/Rad54<sup>-/- </sup>after irradiation was studied<sup> </sup>. Exponentially growing cells were treated for 1 hr with 5 mM WA and then exposed to different doses of X-rays. Cell survival was studied by clonogenic assay. WA significantly reduced survival of DT40, Ku70<sup>-/-</sup> and Ku70<sup>-/- </sup>/Rad54<sup>-/-</sup>, but not Rad54<sup>-/- </sup>cells, suggesting that WA enhances radiosensitivity by interfering with homologous repair, the major pathway of DSB repair in these cells. Inhibition of DNA repair is further indicated in a significant decrease in surviving fraction of DT40 cells by post-irradiation incubation with WA. This could have relevance to cancer radiotherapy.|
|Appears in Collections:||IJEB Vol.46(06) [June 2008]|
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