GASTRIC FORMATION OF N-NITROSO COMPOUNDS IN THE PIG

长期目标：阐明老年人的饮食和生理变量 内源性N-亚硝基化合物的形成使体内形成 这些致癌物质可以通过饮食减少或消除。 修改。其结果将是人类患癌症的风险降低。 具体目标：1)量化诱变剂的内源形成和 胃消化过程中致癌的N-亚硝基化合物及其关系 这些比率对体内非致癌标志物的形成有影响 亚硝化(亚硝基)。2)确定胃是否是鞋底 内源亚硝化的部位和内源前体的重要性 (硝酸盐和胺)与饮食前体的比较。3)量化 抗坏血酸的抑制作用及时间效应的测定 前体和抑制剂的给药。4)确定是否 反式亚硝化作用有助于体内N-亚硝基化合物的形成。5) 测定胃液酸碱度和细菌定植对肠道细菌生长的影响 活体N-亚硝化。6)比较“高”和“低”胃癌风险 在消化过程中形成诱变剂和N-亚硝基化合物的食物。 方法：4头体重为20-70公斤的猪，通过手术植入胃 瘘管将用已知的内源性胺类或酰胺类前体治疗 N-亚硝基化合物和已知或怀疑的亚硝化剂。稳定 将利用前体的同位素。一种不可吸收的标记将是 以已知浓度添加到胃内容物中，从而使体积 可以确定胃内容物丢失到下尿路的情况。胃部 体液样本每隔30分钟用导尿管取出4小时 在测试后给药，并在大多数实验中进行定量分析 对于标志物，致突变活性(细菌)，挥发性N-亚硝基 化合物，N-亚硝基氨基酸，NO3-，NO2-，N-亚硝基甲基脲， 抗坏血酸和同位素比率。在一些实验中，动物将被 在不同的相对时间和不同的抗坏血酸处理 在给予N-亚硝基前体之前的数量。生理学 变量将通过改变胃的酸碱度和建立 胃细菌菌落。高盐鱼干，腌制猪肉， 从小麦中提取的复合淀粉，不存在于叶类蔬菜、水果和 维生素C将被比作含有新鲜水果和 蔬菜。每种食物的胃内容物都会被检测出来。

Long-term Objective: Elucidation of dietary and physiological variables in endogenous N-nitroso compound formation so that the in vivo formation of these carcinogens can be reduced or eliminated through dietary modification. The result will be a diminished human cancer risk. Specific Aims: 1) To quantify endogenous formation of mutagens and carcinogenic N-nitroso compounds during gastric digestion and to relate these rates to the formation of noncarcinogenic markers of in vivo nitrosation (nitrosoproline). 2) To determine if the stomach is the sole site of endogenous nitrosation and the importance of endogenous precursors (nitrate and amines) compared to dietary precursors. 3) To quantify the inhibitory effects of ascorbic acid and to determine the effect of the time of administration of precursors and inhibitor. 4) To determine if transnitrosation contributes to in vivo N-nitroso compound formation. 5) To determine the effects of stomach pH and bacterial colonization on in vivo N-nitrosation. 6) To compare "high" and "low" gastric cancer risk foods for mutagen and N-nitroso compound formation during digestion. Methodology: Four 20 to 70 kg pigs with surgically implanted stomach fistula will be treated with known amine or amide precursors of endogenous N-nitroso compounds and known or suspected nitrosating agents. Stable isotopes of precursors will be utilized. A nonabsorbable marker will be added to the gastric contents at a known concentration so that the volume of gastric contents lost to the lower tract can be determined. Gastric fluid samples will be withdrawn by catheter at 30 min intervals for 4 hours after test administration and in most experiments quantitatively analyzed for the marker, mutagenic activity (bacterial), volatile N-nitroso compounds, N-nitrosoamino acids, NO3-, NO2-, N-nitrosomethylurea, ascorbate, and isotopic ratios. In some experiments, animals will be treated with ascorbic acid at various relative times and with different amounts prior to administration of N-nitroso precursors. Physiological variables will be tested by altering the stomach pH and by establishing gastric bacterial colonies. "Meals" high in salted dried fish, cured pork, complex starches from wheat and absent in leafy vegetables, fruits and vitamin C will be compared to meals containing fresh fruits and vegetables. Gastric contents from each food type will be assayed.