Effects of sodium selenite on deoxycholic acid-induced hyperproliferation of human colonic mucosa in short-term culture

It has been shown that in vitro incubation of human colonic biopsies with t he secondary bile acid deoxycholic acid (DCA) leads to the hyperproliferati on of colonic crypt cells with an expansion of the proliferative zone, whic h is regarded as a biomarker of increased cancer risk. Sodium selenite (SSE ), on the other hand, has been implicated as a protective agent in experime ntal studies, but toxic effects were reported as well, depending on the dos e of SSE. To elucidate the effects of SSE on human colonic mucosa, biopsies from endoscopically normal sigmoid colon tissue of 30 subjects were incuba ted with 5 mu M DCA or a combination of 5 mu M DCA and SSE in concentration s of 5, 10, 20, 50, 80, and 100 mu M, respectively. Equimolar NaCl incubati ons served as a control. Proliferating cells were labeled by bromodeoxyurid ine immunohistochemistry, and the labeling index (LI) was computed. In the experiments using 5, 10, and 20 mu M SSE, the whole crypt LI was significan tly 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 incubatio n were comparable to the LIs obtained after NaCl incubation (average LI = 0 .14). Contrary to this finding, severe cell damage was observed in the biop sies that were incubated with the higher SSE concentrations of 50 mu M and above. The antiproliferative effects of SSE may indicate a possible protect ive effect in the prevention of human colon cancer development. However, th e observed toxic effects of higher SSE concentrations strongly suggest the need for additional studies before general recommendations for the use of S SE in colon cancer prevention can be made.