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Effects of carcinogenic amino-gamma-carbolines on the cell toxicity

致癌氨基-γ-咔啉对细胞毒性的影响

基本信息

批准号：
03454201
负责人：
WADA Osamu
金额：
$ 4.48万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454201/
关键词：
Carcinogen Smooth muscle Platelet Lymphocyte Amino-gamma-carboline アミノー∂ーカルボリン

项目摘要

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.

最近的研究发现在氨基酸和蛋白质的热解产物中存在一系列新的致突变和致癌的杂环胺。其中一些已被证明存在于各种食品、香烟烟雾凝聚物、空气中的颗粒和雨水中，它们被认为广泛分布于环境中。色氨酸- p- 1和色氨酸- p- 2最初是作为强效诱变剂从色氨酸的热解产物中分离出来的，随后在熟食和香烟烟雾凝聚物中检测到。用这种饲料喂养时，Trp-P-1和T-P-2对小鼠和大鼠具有致癌性。最近，我们的观察发现，在尿毒症患者的透析液等人体样本中，以及白内障晶状体、尿液、胆汁和代谢器官中都存在Trp-P-1和Trp-P-2，这表明人类实际上暴露于这些致癌物中。在本研究中，我们检测了致癌物质色氨酸- p- 1和色氨酸- p- 2对牛血管平滑肌细胞和人血小板和淋巴细胞刺激反应系统的影响。Trp-P-1和Trp-P-2通过激活钙调素-肌球蛋白轻链激酶引起血管平滑肌细胞收缩，通过阻断环加氧酶抑制人血小板中TxB_2的产生，抑制PHA诱导的人淋巴细胞增殖。综上所述，这些观察结果表明，Trp-P-1和Trp-P-2不仅具有致癌作用，而且具有细胞功能特异性作用。