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LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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CHAPTER 4<br />

DISCUSSION<br />

different from gamma irradiation, signaling component and intensity of activation will be<br />

different by both types of irradiation. These kinases play an important role in repair, cell cycle<br />

arrest and apoptosis. However, only 11% survival after high LET radiation suggests that most of<br />

the damage could not be repaired and that the persistent activation of these kinases may be a<br />

signature for activation of apoptotic responses. Further studies in this direction will reveal the<br />

importance of such response.<br />

4.4 Radiation induced bystander signaling in mammalian cells.<br />

The signaling events seen in totality in the foregoing work may have contribution from the<br />

surrounding microenvironment that is of necessity exposed to radiation. The cells nearby which<br />

are not directly exposed to the radiation but are juxtaposed to the irradiated cells are also affected<br />

because of signals transduced from the ‘hit’ cell. The classical paradigm of radiation biology<br />

asserts that all radiation effects on cells, tissues and organisms are due to the direct action of<br />

radiation. However, there has been a recent growth of interest in the indirect actions of radiation<br />

including the radiation-induced adaptive response, the bystander effect, low-dose<br />

hypersensitivity, and genomic instability, which are specific modes of stress exhibited in<br />

response to low-dose/low-dose rate radiation.<br />

Radiation-induced bystander signals (whether observed through use of medium harvested from<br />

irradiated cells, or through observation of non-hit cells in contact with irradiated cells), appear to<br />

coordinate tissue or population responses so that cells not directly exposed or traversed by<br />

radiation show responses, which may be part of higher order homeostatic control. Bystander<br />

effects appear to be the result of a generalized stress response in tissues or cells. The signals may<br />

be produced by all exposed cells but the response may require a quorum in order to be expressed.<br />

203

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