Exposure Level Monitor of Carcinogenic Tryptophan Pyrolysis Products in Humans.

人类致癌色氨酸热解产物的暴露水平监测。

• 批准号: 02454198
• 负责人: MANABE Shigeo
• 金额: $ 3.9万
• 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: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454198/
• 关键词: Carcinogen; Mutagen; Tryptophan Pyrolysates; Exposure Monitor; 変異原性

In order to determine a suitable indicator for estimating the exposure levels of the environmental carcinogen, carcinogenic tryptophan pyrolysis products, the levels of these carcinogens in plasma, platelets and red blood cells (RBC) were monitored for 12 weeks by a high-performance liquid chromatography method after these carcinogens were administered as single oral doses (2-20 mg) to rabbits. The results indicate that carcinogenic tryptophan pyrolysis products in RBC that bound covalently to the hemoglobin is the most suitable for monitoring the long-term exposure levels. Moreover, it has been demonstrated that these carcinogens are easily released from hemoglobin adducts by acid (0.5N HCI) treatment at 60ﾟC. Based on these findings obtained in animal experiments, the method is applied for monitoring the exposure levels of carcinogenic tryptophan pyrolysis products in humans. The total number of subjects studied was 16, of whom 8 were healthy normal subjects and 8 were uremic patients treated with hemodialysis. Levels of carcinogenic tryptophan pyrolysis products ih plasma and RBC of these subjects were determined. In both uremic patients and normal subjects, these carcinogens have been detected in RBC as well as plasma. Moreover, these carcinogen levels in RBC (per hemoglobin) were significantly elevated in uremic patients. These results support the idea that these carcinogens. in RBC are suitable for monitoring exposure levels in humans.

为了确定一个合适的指标，以估计暴露水平的环境致癌物，致癌色氨酸热解产物，血浆，血小板和红细胞（RBC）中的这些致癌物的水平进行了监测后，这些致癌物作为单次口服剂量（2-20毫克）的兔子12周的高效液相色谱法。结果表明，红细胞中与血红蛋白共价结合的致癌色氨酸热解产物最适合用于监测长期暴露水平。此外，已经证明，这些致癌物质在60 ℃下通过酸（0.5N HCl）处理很容易从血红蛋白加合物中释放出来。基于动物实验中的这些发现，该方法被应用于监测致癌色氨酸热解产物在人体中的暴露水平。研究的受试者总数为16例，其中8例为健康正常受试者，8例为接受血液透析治疗的尿毒症患者。测定这些受试者血浆和红细胞中致癌色氨酸热解产物的水平。在尿毒症患者和正常受试者中，这些致癌物质已在RBC和血浆中检测到。此外，这些致癌物质在红细胞中的水平（每血红蛋白）显着升高尿毒症患者。这些结果支持了这些致癌物质。适用于监测人体接触水平。

项目成果

S.Manabe et al.: "Detection of a carcinogen,2-amino-1-methy1-6-phenyl-imidazo|4,5-b|pyridine(PhIP)in cigarette smoke" Carcinogenesis. 12. 1945-1947 (1991)

S.Manabe 等人：“香烟烟雾中致癌物 2-氨基-1-甲基1-6-苯基-咪唑|4,5-b|吡啶 (PhIP) 的检测”致癌作用。

S. Manabe et al.: "Detection of Carcinogenic Amino-a-carbolines and Amino-r-Carbollines in Diesel-exhaust Particles." Environ. Pollution. 70. 255-265 (1991)

S. Manabe 等人：“柴油机尾气颗粒中致癌性氨基-α-咔啉和氨基-r-咔啉的检测”。

S.Manabe et al.: "Pharmaco-toxicological aspects of carcinogenic tryptophan pyrolysis products in the environment." J.Envion.Sci.&Health. A26. 1449-1469 (1991)

S.Manabe 等人：“环境中致癌色氨酸热解产物的药理学毒理学方面。”

S.Manabe et al.: "Pharmacoーtoxicological aspects of carcinogenic tryptophan pyrolysis products in the environment." J.Environ.Sci.& Health. A26. 1449-1469 (1991)

S.Manabe 等人：“环境中致癌色氨酸热解产物的药理学方面。”J.Environ.Sci.& Health 1449-1469。

S.Manabe et al.: "Elevation of levels of carcinogenic tryptophan pyrolysis products in plasma and red blood cells of patients with uremia." Clin.Nephrol.

S.Manabe 等人：“尿毒症患者血浆和红细胞中致癌色氨酸热解产物的水平升高。”