LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

PREAMBLE
SYNOPSIS
Ionising radiation leads to a cascade of signaling events which include activation
of alarm signals, cytotoxic and cytoprotective signaling pathways, nitric oxide production
etc. These events culminate in the death or survival of the irradiated cell. The end result
seems to depend upon the pathway predominantly activated. Minute observation of these
complex signaling networks reveals that this is not a random activation of all the
pathways but a very specific, organized and regulated process that is controlled at
multiple steps.
The cellular responses to various forms of radiation are manifested as irreversible
and reversible structural and functional changes in cells and cell organelles. A widely
held view is that the initial reaction of a cell to DNA damage is to repair the damage.
However, with increasing levels of DNA damage the cell switches to cell cycle arrest or
to apoptosis. Cell cycle arrest is sometimes permanent, but ordinarily reversible allowing
time for further DNA repair.
The fact that radiation can lead to cell death has long been exploited effectively in
the therapy of cancer. However, the survival of the radioresistant cell has been the major
drawback of radiotherapy which is delivered in fractionated doses and the cells surviving
the initial dose tend to develop radioresistance making them refractory to subsequent
doses of radiation. Fractionated irradiation induced signaling has not been studied in
detail.
The work embodied in this thesis has been divided into five chapters.
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. References
CHAPTER 1: INTRODUCTION
The first chapter is a general introduction to radiation induced signaling with a historical
perspective on radiation biology. It scans the development of radiation biology and also
reviews the current literature relevant to the work embodied in this thesis. It also lists the
aims and objectives of the present work. A brief overview of the chapter is outlined
below.
Viewed historically, all radiation science is recent, proving that science does
indeed make giant strides in a brief period. Roentgen in the year 1895 initiated the
process by announcing the discovery of a “new kind of penetrating ray” or x-rays [1].
This was followed soon after by Becquerel’s discovery of natural radioactivity in 1896
[2]. Unfortunately the biological effects of ionising radiation and radioactivity lay
unexplored for quite some time after Roentgen’s initial report [3].
When a radiation beam passes through a biological material or other absorbing
media, some energy is imparted to the medium while some of it leaves the volume of
interaction. The absorption of energy from radiation may lead to either excitation or
ionisation. Radiations which lead to the latter effect are called ionising radiation and can
be further classified into electromagnetic and particulate. Ionising radiation can directly
interact with and damage the target molecule. This is known as the direct effect. If it
interacts with the medium to produce secondary particles which, in turn, damages the
target molecule, then it is known as indirect effect.
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