Suzuki H, Iijima K, Moriya A, McElroy K, Scobie G, Fyfe V, McColl K E L
Section of Medicine, Gardiner Institute, Western Infirmary, Glasgow, UK.
Gut. 2003 Aug;52(8):1095-101. doi: 10.1136/gut.52.8.1095.
Saliva has a high nitrite concentration, derived from the enterosalivary recirculation of dietary nitrate, and is the main source of nitrite entering the acidic stomach. Acidification of nitrite in the presence of secondary amines or amides generates potentially carcinogenic N-nitroso compounds. The reaction is inhibited by ascorbic acid and catalysed by thiocyanate.
To determine whether there is intragastric regional variation in the chemical conditions promoting luminal nitrosation following nitrate ingestion.
Using microdialysis probes, we measured concentrations of nitrite, ascorbic acid, total vitamin C, and thiocyanate simultaneously in saliva, the distal oesophagus, cardia, and the proximal and distal stomach of 17 healthy volunteers before and following intragastric nitrate (2 mmol) administration.
The median pH in the distal oesophagus, cardia, and proximal and distal stomach were 7, 2.6, 1.9, and 1.7, respectively, before, and were similar following nitrate administration. Mean nitrite concentration in the distal oesophagus was similar to that of saliva, being 29.1 micro M and 36.7 micro M, respectively, before nitrate and increasing to 181.6 micro M and 203.3 micro M after nitrate ingestion. Within the stomach, mean (SEM) nitrite concentration following nitrate was higher in the cardia (45.5 (12.7) micro M) than in the mid (7.8 (3.1)) (p<0.01) or distal (0.8 (0.6)) (p<0.1) stomach, and ascorbic acid concentration was lower at the cardia (13.0 (6.1)) than in the mid (51 (19.2)) (p<0.02) or distal (86 (29)) (p<0.01) stomach. Consequently, the median ascorbic acid to nitrite ratio was lowest at the cardia (0.3) (p<0.01) versus the mid (7.8) or distal (40) stomach. Thiocyanate concentration was similar throughout the stomach.
The conditions favouring luminal generation of N-nitroso compounds from dietary nitrate are maximal at the most proximal cardia region of the acidic stomach and may contribute to the high incidence of mutagenesis at this site.
唾液中亚硝酸盐浓度较高，来源于膳食硝酸盐的肠-唾液再循环，是亚硝酸盐进入酸性胃的主要来源。在仲胺或酰胺存在的情况下，亚硝酸盐的酸化会生成潜在致癌的N-亚硝基化合物。该反应受抗坏血酸抑制，受硫氰酸盐催化。
确定摄入硝酸盐后，促进腔内亚硝化作用的化学条件在胃内是否存在区域差异。
使用微透析探针，我们在17名健康志愿者胃内给予硝酸盐（2 mmol）之前和之后，同时测量了唾液、食管远端、贲门以及胃近端和远端的亚硝酸盐、抗坏血酸、总维生素C和硫氰酸盐的浓度。
食管远端、贲门以及胃近端和远端的pH中位数在给予硝酸盐之前分别为7、2.6、1.9和1.7，给予硝酸盐后相似。食管远端的平均亚硝酸盐浓度与唾液相似，在给予硝酸盐之前分别为29.1 μM和36.7 μM，摄入硝酸盐后分别增加到181.6 μM和203.3 μM。在胃内，摄入硝酸盐后贲门处的平均（标准误）亚硝酸盐浓度（45.5（12.7）μM）高于胃中部（7.8（3.1））（p<0.01）或胃远端（0.8（0.6））（p<0.1），贲门处的抗坏血酸浓度（13.0（—6.1））低于胃中部（51（19.2））（p<0.02）或胃远端（86（29））（p<0.01）。因此，贲门处抗坏血酸与亚硝酸盐的中位数比值最低（0.3）（p<0.01），而胃中部为7.8，胃远端为40。硫氰酸盐浓度在整个胃内相似。
有利于由膳食硝酸盐在腔内生成N-亚硝基化合物的条件在酸性胃的最近端贲门区域最为显著，这可能是该部位诱变高发的原因。
