LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

CHAPTER 4
DISCUSSION
The major response involving low LET radiation exposure discussed in the existing literature is a
death response, which has many characteristics of apoptosis but may be detected in cell lines
without p53 expression [285].
Two main models have emerged concerning the mechanisms of bystander mediated responses,
mainly based on the way the experiments were performed and the cell type selected for
investigation. They are communication via gap junction intercellular communication (GJIC) and
communication via media-borne or transmissible factors [286-289] (Fig. 1.6).
The present study was carried out to investigate what genes and proteins are activated in the
bystanding cell and whether the state of activation of the irradiated cell alters the bystander
response. The results revealed that there was significant decrease in the survival of bystander
A549 cells and significant increase in γ-H2AX and pATM foci but only in those cells that had
received medium from irradiated cells (Fig.3.4.1). Since the cells treated only with irradiated
medium did not show any change in survival or γ-H2AX and pATM foci the signals which
caused the damage in the bystander cells must be coming from the irradiated cells themselves.
Having confirmed the existence of bystander effect between similar cells (A549 Vs
A549), the work was extended to look for the existence of cross bystander effect between A549
and U937 cells i.e. lung carcinoma and monocytes. There was a significant decrease in the
survival of A549 cells that had received medium from PMA stimulated and irradiated U937 cells
(Fig.3.4.2) and expectedly the γ-H2AX and pATM foci were also significantly higher in these
cells (Fig.3.4.2). A549 cells that had received medium from either irradiated or PMA stimulated
U937 cells did not show bystander response, indicating the fact that activation of U937 was prerequisite
for the induction of cross bystander response. The PMA treatment of monocytes
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