Tumor cell apoptosis by irradiation-induced nitric oxide production in vascular endothelium

Masakazu Hirakawa, Masahiro Oike, Kouji Masuda, Yushi Ito

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19 Citations (Scopus)


We examined the effects of X-ray irradiation on endothelial nitric oxide (NO) production in bovine aortic endothelial cells (BAECs). Single irradiation of up to 60 Gy did not affect the expression of endothelial NO synthase (eNOS) mRNA, as assessed by reverse transcription-PCR, in BAECs. The basal level of intracellular Ca2+ concentration and Ca2+ mobilization induced by thapsigargin and ATP were also not affected by single irradiation. However, eNOS-mediated, Ca2+-dependent constitutional NO production could not be examined directly because irradiated BAECs showed continuous NO production, as measured by diaminofluorescein-2 fluorescence, without agonist stimulation. Expression of inducible NO synthase (iNOS) mRNA and protein was markedly increased by 2 Gy of irradiation, thereby indicating that the basal and continuous NO production in irradiated BAECs was due to the expression of iNOS. Hepatoma HepG2 cells cocultured with irradiated BAECs showed apoptosis in the presence of L-arginine, and the apoptosis was prevented by L-NAME (Nω-nitro-L-arginine methyl ester). These results indicate that single irradiation does not affect Ca2+ mobilization and eNOS expression but induces the expression of iNOS in BAECs, and the latter property would be beneficial to induce apoptosis in the adjacent tumor cells.

Original languageEnglish
Pages (from-to)1450-1457
Number of pages8
JournalCancer Research
Issue number5
Publication statusPublished - Mar 1 2002

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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