title: Role of iNOS in bystander signaling between macrophages and lymphoma cells.
abstract: 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.
authors.affiliation: Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Somnath
authors.initials: S
authors.lastname: Ghosh
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Maurya
authors.forename: Malini
authors.initials: M
authors.lastname: Krishna
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm; D004247:DNA; D052247:Nitric Oxide Synthase Type II