Bartram H P, Draenert R, Dusel G, Richter F, Liebscher E, Christl S U, Scheppach W, Kasper H
Practice for Gastroenterology, Augsburg, Germany.
Cancer Epidemiol Biomarkers Prev. 1998 Dec;7(12):1085-9.
It has been shown that in vitro incubation of human colonic biopsies with the secondary bile acid deoxycholic acid (DCA) leads to the hyperproliferation of colonic crypt cells with an expansion of the proliferative zone, which is regarded as a biomarker of increased cancer risk. Sodium selenite (SSE), on the other hand, has been implicated as a protective agent in experimental studies, but toxic effects were reported as well, depending on the dose of SSE. To elucidate the effects of SSE on human colonic mucosa, biopsies from endoscopically normal sigmoid colon tissue of 30 subjects were incubated with 5 microM DCA or a combination of 5 microM DCA and SSE in concentrations of 5, 10, 20, 50, 80, and 100 microM, respectively. Equimolar NaCl incubations served as a control. Proliferating cells were labeled by bromodeoxyuridine immunohistochemistry, and the labeling index (LI) was computed. In the experiments using 5, 10, and 20 microM SSE, the whole crypt LI was significantly lower after DCA + SSE incubation (0.136, 0.118, and 0.110, respectively) compared to that after incubation with DCA alone (0.172, 0.157, and 0.165, respectively; P < 0.01). The corresponding LIs during DCA + SSE incubation were comparable to the LIs obtained after NaCl incubation (average LI = 0.14). Contrary to this finding, severe cell damage was observed in the biopsies that were incubated with the higher SSE concentrations of 50 microM and above. The antiproliferative effects of SSE may indicate a possible protective effect in the prevention of human colon cancer development. However, the observed toxic effects of higher SSE concentrations strongly suggest the need for additional studies before general recommendations for the use of SSE in colon cancer prevention can be made.
研究表明，人结肠活检组织在体外与次级胆汁酸脱氧胆酸（DCA）一起孵育会导致结肠隐窝细胞过度增殖，增殖区扩大，这被视为癌症风险增加的生物标志物。另一方面，亚硒酸钠（SSE）在实验研究中被认为是一种保护剂，但也有报道称其存在毒性作用，这取决于SSE的剂量。为了阐明SSE对人结肠黏膜的影响，将30名受试者内镜检查正常的乙状结肠组织活检标本分别与5微摩尔DCA或5微摩尔DCA与浓度分别为5、10、20、50、80和100微摩尔的SSE的组合一起孵育。等摩尔氯化钠孵育作为对照。通过溴脱氧尿苷免疫组织化学标记增殖细胞，并计算标记指数（LI）。在使用5、10和20微摩尔SSE的实验中，与单独用DCA孵育后相比（分别为0.172、0.157和0.165；P<0.01），DCA+SSE孵育后整个隐窝LI显著降低（分别为0.136、0.118和0.110）。DCA+SSE孵育期间相应的LI与氯化钠孵育后获得的LI相当（平均LI=0.14）。与这一发现相反，在与50微摩尔及以上较高SSE浓度孵育的活检标本中观察到严重的细胞损伤。SSE的抗增殖作用可能表明其在预防人类结肠癌发生方面具有潜在的保护作用。然而，较高SSE浓度所观察到的毒性作用强烈表明，在就SSE用于预防结肠癌提出一般性建议之前，需要进行更多研究。
