ESTABLISHING THE BASIC OF THE NITROSOPROLINE TEST

建立亚硝基脯氨酸测试的基础

• 批准号: 3548862
• 负责人: SIDNEY S MIRVISH
• 金额: $ 16.19万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3548862
• 关键词: diet; dietary proteins; gastrointestinal toxin absorption; human subject; lymphoma; nitrates; nitrosamines; nitroso compounds; nutrition related tag; proline; toxin metabolism; urinalysis; vegetables; water pollution

Nitrate levels in water are increasing in the U.S.A, mainly because of runoff from fertilized agricultural land. Hence hazards due to excess nitrate are a consequence of the agricultural industry and are of special interest to E.P.A. At nitrate levels above 50 mg/l, drinking water becomes the main source of exposure to nitrate. Nitrate exposure presents a hazard, because intragastric nitrite can react with amines and amides to form N-nitroso compounds (NNC), which could cause cancer. Ohshima and Bartsch developed a test for measuring in vivo nitrosamine formation, in which proline and nitrate are ingested and N-nitrosoproline (NPRO) is determined in urine. By giving proline without nitrate, this test can be used to measure potential for in vivo nitrosation. This potential depends on intragastric levels of nitrite and nitrosation modifiers, and other factors. The proposed research and future epidemiologic studies will help establish the basis of this test and help answer the questions: Could an elevated exposure to nitrate, especially in drinking water, produce abnormally high levels in vivo of NNC under specified conditions? What nitrate level produces a significant level of NNC? Does this nitrate level vary between countries and with diet? How is NNC formation modified by dietary ascorbate (ASC), vegetables, and macronutrients? Accordingly, we will measure NPRO excretion in the urine of volunteers, after they consume L-proline and varying nitrate levels in drinking water, measure the variability of NPRO excretion, ensure that NPRO is formed endogenously, and determine how nitrate, ASC, vegetables, proteins and other macronutrients influence NPRO formation. These studies (with support from rat experiments) will determine protocols for future epidemiologic studies. We will measure NPRO content of the food, nitrate excretion in urine; nitrate nitrite and thiocyanate levels in saliva; nitrate in drinking water; and nitrate, nitrite and ASC in diet. We will apply these tests to farmers from the Kearney area of Nebraska and to lymphoma patients in remission, who drink high- and low-nitrate water.

美国水中的硝酸盐含量不断增加，主要原因是 来自施肥农田的径流。 因此，过量会带来危险 硝酸盐是农业的产物，具有特殊的性质 环保署的兴趣 当硝酸盐含量超过 50 毫克/升时，饮用水会变成 接触硝酸盐的主要来源。 硝酸盐暴露会导致 危险，因为胃内的亚硝酸盐可以与胺和酰胺反应， 形成 N-亚硝基化合物 (NNC)，可能致癌。 大岛和 Bartsch 开发了一种测量体内亚硝胺形成的测试， 脯氨酸和硝酸盐被摄入，N-亚硝基脯氨酸（NPRO）是 尿液中测定。 通过给予不含硝酸盐的脯氨酸，该测试可以 用于测量体内亚硝化的潜力。 这种潜力取决于 亚硝酸盐和亚硝化调节剂的胃内水平，以及其他 因素。 拟议的研究和未来的流行病学研究将有助于 建立该测试的基础并帮助回答以下问题： 大量接触硝酸盐，尤其是饮用水中的硝酸盐，会产生 在特定条件下体内 NNC 水平异常高？ 什么 硝酸盐水平会产生显着水平的 NNC？ 这个硝酸盐含量是多少 因国家和饮食习惯而异？ NNC 形成如何修改 膳食抗坏血酸 (ASC)、蔬菜和常量营养素？ 据此，我们 将测量志愿者服用后尿液中 NPRO 的排泄量 饮用水中的 L-脯氨酸和不同的硝酸盐含量，测量 NPRO 排泄的可变性，确保 NPRO 是内源形成的，并且 确定硝酸盐、ASC、蔬菜、蛋白质和其他常量营养素的含量 影响NPRO的形成。 这些研究（在大鼠的支持下 实验）将确定未来流行病学研究的方案。 我们 会测量食物中的NPRO含量、尿液中硝酸盐的排泄量；硝酸盐 唾液中亚硝酸盐和硫氰酸盐的含量；饮用水中的硝酸盐；和 饮食中的硝酸盐、亚硝酸盐和 ASC。 我们将把这些测试应用于农民 来自内布拉斯加州科尔尼地区和缓解期淋巴瘤患者， 谁喝高硝酸盐水和低硝酸盐水。