LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

CHAPTER 4
DISCUSSION
upregulates many genes in the monocyte hence their response to irradiation will be different
from unstimulated monocyte.
Having confirmed that bystander effect contributed the survival of the neighbouring cells, the
lung carcinoma A549 cells, the mechanism of bystander effect and the factor involved in the
bystander effect was studied in mouse cell line.
The present results revealed a significant increase in DNA damage in the bystander cells but only
in those cells that had received medium from irradiated cells (Fig.3.4.3.3). Since the cells treated
only with irradiated medium did not show any DNA damage or NO production, the signals
which caused the damage in the bystander cells must be coming from the irradiated cells
themselves. The expression of cell cycle related genes (p53 and p21) was significantly
upregulated in bystander similar cells (Fig.3.4.3.1C and D, Lane 3). These results are in
agreement with the work on bystander signaling [290, 291]. The first report describing the
induction of sister chromatid exchanges (SCE) was examined in Chinese hamster ovary (CHO)
cells. Since CHO cells contain mutant p53, therefore, p53 could not be involved in the bystander
induction of SCE [220]. If the p53 of the bystander cell is mutated there should be less DNA
repair and in fact more bystander effect can be seen when assessed in terms of DNA damage.
A clear cause and effect relationship was established between DNA damage, gene expression
and cell survival and was evident in the form of increase apoptosis in bystander cells (Fig.
3.4.3.4a, Lane 3 and Fig. 3.4.3.4b).
An increased expression of NF-κB gene (p65) could lead to the activation of iNOS gene since
the promoter of the iNOS gene contains binding sites for NF-κB. NF-κB is known to be
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