Vermeer I T, Engels L G, Pachen D M, Dallinga J W, Kleinjans J C, van Maanen J M
Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands.
Gastroenterology. 2001 Sep;121(3):517-25. doi: 10.1053/gast.2001.27098.
BACKGROUND & AIMS: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters.
Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts.
The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium.
Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients.
本研究评估了长期使用奥美拉唑进行胃酸抑制治疗对胃内致癌性N-亚硝胺水平及相关参数的影响。
45例长期服用奥美拉唑的患者(平均35个月)和13例未服药的健康受试者参与研究。测定胃液和尿液中的挥发性N-亚硝胺。测定胃内pH值、亚硝酸盐、硝酸盐及幽门螺杆菌状态。分析从胃活检标本中分离的DNA的致癌前体烷基-DNA加合物。
与对照组相比,患者的胃内pH值显著更高(P = 0.0001)。患者的胃内亚硝酸盐水平略高,但无统计学意义。患者与对照组胃内挥发性N-亚硝胺的总水平无差异,然而,患者的尿中N-亚硝基二甲胺排泄量更高(P = 0.001)。在服用奥美拉唑的情况下,幽门螺杆菌阳性与阴性患者的胃内亚硝酸盐水平略高,尿中N-亚硝基二甲胺排泄量更高。胃上皮中未检测到烷基-DNA加合物。
长期使用奥美拉唑导致胃内pH值升高并不会导致胃内亚硝酸盐和挥发性N-亚硝胺水平升高。尿中N-亚硝胺排泄量显著更高意味着在长期奥美拉唑治疗期间内源性N-亚硝胺形成增加的风险。这种风险在幽门螺杆菌阳性患者中可能更高。