LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

18 S. Ghosh et al. / Mutation Research 716 (2011) 10–19
Since, with high LET radiation yield of ROS is very low as compared
to low LET radiation [38–40], the early activation of ERK was
not expected with high LET radiation. However, complete absence
of ERK activation even hours after high LET radiation suggests that
repair pathways are neither feeding into nor being fed upon by
intracellular cytoprotective signaling. However, the pro-apoptotic
JNK pathway was found to be activated after high LET radiation.
BRCA1 induced apoptotic responses have also been shown to be
via activation of JNK [41]. Thus, after carbon irradiation, DNA damage
induced activation of repair components are being fed into
by cytotoxic signaling rather than cytoprotective responses and
was evident in the form of early induction of apoptosis (Fig. 8).
Since, cellular decisions are summation of all the activated pathways,
the final response after high LET radiation tips towards
death.
5. Conclusions
In summary, our results suggest that the subtle differences
leading to different outcomes due to radiation quality seem to
lie in different macromolecular complexes of crucial DNA damage
response proteins and activation of other intracellular pathways
in A549 lung adenocarcinoma cell line. Analysis of functionality of
these macromolecular complexes as a whole rather than individual
proteins and holistic study involving intracellular survival pathways
could help in revealing the mechanistic details of complex
DNA damage responses.
Conflict of interest
The authors declare that there are no conflicts of interest.
Acknowledgments
This work was funded by Board of Research in Nuclear Sciences,
Department of Atomic Energy [DAE], Government of India, through
a project sanctioned to one of the authors, A. Sarma, bearing sanction
number 2007/37/37/BRNS. All the authors are thankful to the
Director, IUAC, New Delhi for providing radiation facility for the
work. We would also like to extend our thanks to all the members
of Pelletron group of IUAC and Harminder Kaur, Radiation Biology
Laboratory, IUAC for their sincere help during irradiation. 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.
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