LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

CHAPTER 4
DISCUSSION
directly exposed to the radiation but are juxtaposed to the irradiated cells are also affected
because of signals transduced from the ‘hit’ cell. The classical paradigm of radiation biology
asserts that all radiation effects on cells, tissues and organisms are due to the direct action of
radiation. However, there has been a recent growth of interest in the indirect actions of radiation
including the radiation-induced adaptive response, the bystander effect, low-dose
hypersensitivity, and genomic instability, which are specific modes of stress exhibited in
response to low-dose/low-dose rate radiation.
4.1 Fractionated irradiation induced signaling and repair in mammalian cells.
It is known that cellular response to ionising radiation is a complex phenomenon where the dose,
dose rate and its fractionation play an equally important role in deciding the fate of the cell.
Extensive work has been done and published on the response of the cell to single doses of
radiation which are reflected as lesions in the DNA and non DNA targets. Among the latter are
the signaling proteins that act to signal that the DNA is damaged as well as to regulate processes
such as cell cycle progression and DNA repair. These pathways are also intricately linked with
the intrinsic radioresistance of the cell [237, 238]. In recent years these signaling proteins are
being exploited as targets to enhance tumor radiosensitivity [238-240]. The targets have been
chosen based on their activation following a single dose of radiation. Since signaling, as it is now
known, is not a linear activation of a pathway but a complex network where both positive and
negative signals are activated simultaneously following exposure to stress , it is quite likely that
the signaling factors that are being targeted may not be activated in a cancer cell that has
undergone radiotherapy. The study of the ultimate radioresistant phenotype is undoubtedly a
very important aspect but the immediate response of the signaling factors to repeated doses of
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