1994 Fiscal Year Final Research Report Summary
Endogenous induction of nitrosamines
| Project/Area Number |
05454611
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Osaka University |
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Principal Investigator |
KOSAKA Hiroaki Osaka Univ.Med.Sch., Lecturer, 医学部, 講師 (60158897)
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| Co-Investigator(Kenkyū-buntansha) |
KUMURA Eiji Osaka Univ.Med.Sch., Assist.Prof., 医学部, 助手 (50260633)
SHIGA Takeshi Osaka Univ.Med.Sch., Professor, 医学部, 教授 (10028350)
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| Project Period (FY) |
1993 – 1994
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| Keywords | nitrosamine / nitric oxide (NO) / electron spin resonance / oxygen saturation / hemoglobin / nitric oxide synthase / ischemic-gamma perfusion / allograft rejection |
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| Research Abstract |
To know whcther environmentally existing amins are involved in in vivo nitrosation during inflammation, we studied the effect of interleukin 1 (IL-1) tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) on NO production inrats by detecting NO-hemoglobin (HbNO) in their blood using ESR,since the extent of nitrosation paralleled with NO production. Either IL-1 or TNF alone, but not IFN-gamma alone stimulated NO-hemoglobin (HbNO) generation, demonstrating synorglstic character of both stimuli on NO production. Further, LPS and TNF in combination were more potent stimulator of HbNO production in rats than each alone. Addition of IFN-gamma to the LPS-treated rats increased the TNF release markedly. These suggest that the increase of TNF release by IFN-gamma plays a key role in LPS-trated rats with respect to NO generation. During these experiments, distinct three-line hyperfune structure of HbNO was present in venous blood but not in arterial blood. We cleared that the three-line hyperfine structure intensified lineally with the decrease of oxygen sturation of hemoglobin, but desappeared upon reoxygenation of hemoglobin. We also found that plasma nitrate increases and HbNO appears during rat focal cerebral inschemia and reperfusion. Furthere, we proved using stable isotope of nitrogen that NO generates from nitrovasodilator as a result of metabolism. If nitrosatable amins exist in the environment and if someone is lacking ascorbic acid he may be exposed to the threat of nitrosamine formation by the endogenous NO especially in the case of inflammation.
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[Publications] S.Tanaka, W.Kamiike, T.Ito, S.Nozaki, F.Uchikoshi, M.Miyata, S.Nakata, R.Shirakura, H.Matsuda, E.Kumura, T.Shiga and H.Kosaka: "Elevation of nitric oxide during acute rejection after heart transplantation in rats" Cancer letters. in press.(1995)
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