Role of iNOS in bystander signaling between macrophages and lymphoma cells.
OBJECTIVE
The present report describes the bystander effects of radiation between similar and dissimilar cells and the role of iNOS in such communication.


METHODS
EL-4 and RAW 264.7 cells were exposed to 5 Gy gamma-irradiation. The medium from irradiated cells was transferred to unirradiated cells.


RESULTS
Irradiated EL-4 cells as well as those cultured in the presence of medium from gamma-irradiated EL-4 cells showed an upregulation of NF-kappaB, iNOS, p53, and p21/waf1 genes. The directly irradiated and the bystander EL-4 cells showed an increase in DNA damage, apoptosis, and NO production. Bystander signaling was also found to exist between RAW 264.7 (macrophage) and EL-4 (lymphoma) cells. Unstimulated or irradiated RAW 264.7 cells did not induce bystander effect in unirradiated EL-4 cells, but LPS stimulated and irradiated RAW 264.7 cells induced an upregulation of NF-kappaB and iNOS genes and increased the DNA damage in bystander EL-4 cells. Treatment of EL-4 or RAW 264.7 cells with L-NAME significantly reduced the induction of gene expression and DNA damage in the bystander EL-4 cells, whereas treatment with cPTIO only partially reduced the induction of gene expression and DNA damage in the bystander EL-4 cells.


CONCLUSIONS
It was concluded that active iNOS in the irradiated cells was essential for bystander response.
Ghosh
Somnath
S
Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai, India.
Maurya
Dharmendra Kumar
DK
Krishna
Malini
M
D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000528:radiation effects; D005720:Gamma Rays; D008223:Lymphoma / Q000201:enzymology / Q000503:physiopathology*; D008264:Macrophages / Q000201:enzymology / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects
D004273:DNA, Neoplasm; D004247:DNA; D052247:Nitric Oxide Synthase Type II