| Project/Area Number |
03454201
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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 |
Hygiene
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| Research Institution | University of Tokyo |
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Principal Investigator |
WADA Osamu University of Tokyo, Hygiene and Preventive Medicine Professor, 医学部(医), 教授 (60009933)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGISAWA Hiroyuki University of Tokyo, Hygiene and Preventive Medicine Assistant Professor, 医学部(医), 助手 (10200536)
NAGAHASHI Masaru University of Tokyo, Hygiene and Preventive Medicine Assistant Professor, 医学部(医), 助手 (90009994)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Carcinogen / Smooth muscle / Platelet / Lymphocyte / Amino-gamma-carboline / アミノー∂ーカルボリン |
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| Research Abstract |
Recent investigations have revealed a new series of mutagenic and carcinogenic heterocyclic amines in pyrolysates of amino acid and proteins. Some of them have been demonstrated to be present in various food stuffs, cigarette smoke condensate, airborne particles and rain water, and they are believed to be distributed widely in the environment Trp-P-1 and Trp-P-2 were originally isolated as potent mutagens from pyrolysates of tryptophan and subsequently detected in cooked foods and cigarette smoke condensate. When fed with the diet, Trp-P-1 and T-P-2 are carcinogenic to mice and rats. Recently, our observations showed that Trp-P-1 and Trp-P-2 were present in human samples such as dialysis fluid of patients with uremia, as well as in cataractous lenses, urine, bile and metabolic organs, indicating that humans are actually exposed to these carcinogens.
In the present studies we examined the effects of carcinogenic Trp-P-1 and Trp-P-2 on the stimulus-reaction system in bovine vascular smooth muscle cells and human platelets and lymphocytes. Trp-P-1 and Trp-P-2 caused 1) the vascular smooth muscle cell constriction through the activation of calmodulin-myosin light chain kinase, 2) the inhibition of TxB_2 production in human platelets via the blockade of cyclooxygenase and 3) the inhibition of the human lymphocyte proliferation induced by PHA.Collectively, these observations indicate that Trp-P-1 ant Trp-P-2 have not only the carcinogenic effects but also the effects specific for cell functions.
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