LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

S. Ghosh, M. Krishna / Mutation Research 729 (2012) 61–72 71
explaining the mechanism of such response as activation of repair
pathway, efficient DNA repair and translocation of phospho-p53
into the nucleus of A549 cells exposed to fractionated irradiation
and not in MCF-7 cells exposed to fractionated irradiation (Fig. 7).
Numerous reports have implicated DNA repair genes as being
mainly responsible for the development of radioresistance due to
fractionated irradiation [54,55,57,58]. To investigate what factors
are involved in fractionated irradiation induced radioresistance in
A549 cells, the cells were transfected with either Rad52 or MLH1
shRNA plasmid and exposed to 5 fractions of 2 Gy. The survival of
A549 cells that had been transfected with MLH1 shRNA plasmid
and exposed to fractionated irradiation was found to be 40 ± 1.8%
where as the survival of A549 cells which had been transfected with
Rad52 shRNA plasmid and exposed to fractionated irradiation was
23 ± 1.5% (Fig. 8). The above results demonstrate that the Rad52
gene is one of the factors responsible for the increased radioresistance
in A549 cells if 10 Gy dose was delivered as fractionated
irradiation. These observations strongly argue for the functional
importance of Rad52 in DSB repair in lung adenocarcinoma A549
cells.
5. Conclusions
In summary, our results indicated that A549 cells were relatively
more radioresistant if these cells were exposed to fractionated irradiation.
The reason for radioresistance could be the activation of
DNA repair pathways and Rad52 gene is an important factor modulating
radioresistance in A549 cells. This study contributes basic
information about some of the genes involved in radioresistance
and may eventually contribute to clinical investigations of prediction
markers and prognostic factors, as well as the development of
radiosensitive molecules for therapeutic use.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
Authors would like to thank Mr. Manjoor Ali and Mr. Paresh
Khadilkar, RB&HSD, BARC for their help in Confocal Microscopy and
Lab work respectively.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.mrfmmm.2011.09.007.
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