LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

CHAPTER 4
DISCUSSION
4.3 High LET irradiation induced signaling in mammalian cells and its comparison with
Gamma irradiation.
Although many studies on signaling pathways after low and high LET radiations have found the
activation to be similar except in the intensity [214] but since the end result of the two
irradiations is different, there must be a divergence of pathways at some stage. It is this stage of
signaling, that is different, that will be crucial to designing therapies that target specific
molecules or pathways
4.3.1 Carbon beam induced signaling in mammalian cells and its comparison with Gamma
irradiation.
Although 1Gy dose of carbon ions was three times more toxic to the cells than gamma
rays, both produced same number of γ-H2AX foci, indicators of DNA double strand breaks, the
primary lesions induced by radiation (Fig.3.3.1.1 and Fig.3.3.1.2). This discrepancy between
observed cytotoxicity and estimated γ-H2AX foci after high LET radiation has also been
reported previously [272]. The observed decrease in number of γ-H2AX foci 4 hours after
gamma irradiation indicated that DNA damage induced by low LET was repaired faster than
high LET radiation and is supported by nearly 100% survival. However, the decrease in γ-H2AX
foci after Carbon ion irradiation was definitely not indicative of repair because the cell survival
data contradicts the fact (Fig.3.3.1.2). Since total intensity of γ-H2AX was yet high at 4 hours in
carbon irradiated cells, it indicated diffused staining of γ-H2AX rather than dephosphorylation. It
may represent sites of increased DNA damage arising from misrepair or incomplete repair [273,
274].
196