@misc{oai:repo.qst.go.jp:00069050,
 author = {Katsube, Takanori and Mori, Masahiko and Tsuji, Hideo and Shiomi, Tadahiro and Onoda, Makoto and 勝部 孝則 and 森 雅彦 and 辻 秀雄 and 塩見 忠博 and 小野田 眞},
 month = {Jul},
 note = {Reactive oxygen and nitrogen species (RONS) are generated within cells by ionizing radiation via primary ionizing events as well as through secondary amplification systems including metabolic synthesis. Their high reactivities to a variety of macromolecules within cells not only cause dysfunction of the target molecules but also modulate intra- and inter-cellular signal transduction pathways. Hence, RONS are implicated directly and/or indirectly to play a crucial role in biological effects of ionizing radiation. Extensive studies concerning the inflammatory responses have shown that cellular effects of RONS are much complicated and either detrimental or protective, probably depending on the amount, duration, and site of generation as well as the type of species. To elucidate the molecular mechanisms of RONS in both inflammatory and radiation responses, we examined cellular responses to the relatively low concentrations (lower than 0.1 M) of exogenous H2O2 and NO.
A human intestinal epithelial cell line, Caco-2, were grown on permeable supports and exposed to H2O2 and/or NO donors, such as NOC5 and NOC12. A H2O2 treatment induced tyrosine phosphorylation of numerous cellular proteins including ZO-1, E-cadherin, and beta-catenin, components of cell-cell junctions, and exhibited several remarkable features of cell-cell junctional dysfunction, such as an increase in paracellular permeability and disturbance of morphological architecture of cell-cell junctions. On the other hand, a combined treatment with H2O2 and an NO donor suppressed the protein tyrosine phosphorylation and relieved the damage to the cell-cell junction. These findings suggest the presence of two distinct intracellular signalling pathways for detrimental and protective events mediated by H2O2 and NO, respectively. The latter pathway somehow might attenuate the former. 
 We will also show the latest findings with regard to the effects of H2O2 on radiosensitive mutant cell lines. Targeted disruption of repair genes, such as XRCC4 and Artemis, for DNA double-strand breaks (DSBs) sensitized a human intestinal cancer cell line, HCT116, to ionizing radiation as well as H2O2. Mechanisms underlying DSBs induction by relatively low concentrations of H2O2 (around 0.01-0.04 M) are now under investigation., 13th International Congress of Radiation Research},
 title = {Cytotoxic and cytoprotective signaling pathways mediated by reactive oxygen and nitrogen species},
 year = {2007}
}