GASTRIC FORMATION OF N-NITROSO COMPOUNDS

长期目标：阐明 内源性N-亚硝基化合物的形成，使体内形成的 这些致癌物质可以通过饮食减少或消除， 改性 其结果将是降低人类癌症风险。 具体目的：1）定量致突变物的内源性形成， 致癌的N-亚硝基化合物在胃消化和有关 这些比率与体内非致癌标记物的形成有关， 亚硝化（亚硝基脯氨酸）。 2)以确定胃是否是唯一的 内源性亚硝化位点和内源性前体的重要性 （硝酸盐和胺）与膳食前体相比。 3)量化 抗坏血酸的抑制作用，并确定时间的影响 前体和抑制剂的施用。 4)以确定是否 转亚硝化有助于体内N-亚硝基化合物的形成。 第五章） 为了确定胃pH值和细菌定植对胃肠道的影响， 体内N-亚硝化。 6)比较“高”和“低”胃癌风险 食物在消化过程中形成诱变剂和N-亚硝基化合物。 方法：4只20 - 70 kg猪，手术植入胃 瘘管将用已知的内源性的胺或酰胺前体治疗， N-亚硝基化合物和已知或可疑的亚硝化剂。 稳定 将使用前体的同位素。 将使用不可吸收标记 以已知的浓度添加到胃内容物中， 可以确定胃内容物流失到下消化道的量。 胃 将通过导管以30分钟间隔抽取液体样本，持续4小时 在试验给药后，并在大多数实验中定量分析 对于标记物，诱变活性（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， 抗坏血酸盐和同位素比率。 在一些实验中，动物将被 用抗坏血酸在不同的相对时间和用不同的 在施用N-亚硝基前体之前的量。 生理 将通过改变胃pH值和建立 胃细菌菌落。 "餐"高咸鱼干，腌猪肉， 从小麦中提取的复合淀粉，不存在于多叶蔬菜、水果和蔬菜中。 维生素C将与含有新鲜水果的膳食进行比较， 蔬菜. 将分析每种食物类型的胃内容物。

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 Gastric fluid samples will be withdrawn by catheter at 30 min intervals for 4 hours after test administration and in most experiments quantitatively analyzed for the marker, mutagenic activity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.