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LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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CHAPTER 3<br />

RESULTS<br />

3.3 High LET irradiation induced signaling in mammalian cells and its comparison with<br />

Gamma irradiation.<br />

Having established the signaling differences between proton beam and gamma ray in lung<br />

carcinoma A549 cells, the variance in signaling pattern with higher LET (Carbon and Oxygen)<br />

was studied. Although enough gross evidence exists of the activation of signaling pathways after<br />

irradiation, the differences between gamma and High LET have not been studied in detail. The<br />

two seem to activate the same pathways but must diverge at some point so that the end point can<br />

be different. Many studies on signaling pathways after low and high LET radiations have found<br />

the activation to be similar except in the intensity [214] but since the end result is different, there<br />

must be a divergence of pathways at some stage. It is this stage of signaling, that is different, that<br />

will be crucial to designing therapies that target specific molecules or pathways. The aim of the<br />

present study was to look for these subtle differences that are of immense consequences.<br />

3.3.1 Carbon beam induced signaling in mammalian cells and its comparison with Gamma<br />

irradiation.<br />

Carbon beams are high linear energy transfer (LET) radiation characterized by higher relative<br />

biological effectiveness than low LET radiation. The aim of the current study was to determine<br />

the signaling differences between γ and carbon ion-irradiation. A549 cells were irradiated with<br />

1Gy carbon or γ-radiation and the activation of DNA damage response signaling was studied.<br />

3.3.1.1 Carbon ions were three times more cytotoxic than gamma<br />

To determine the sensitivity of cells to similar dose of high and low LET radiation, their ability<br />

to form colonies after irradiation was observed. Irradiation of exponentially growing A549 cells<br />

144

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