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 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.
Bartram
H P
HP
Practice for Gastroenterology, Augsburg, Germany. HP.Bartram@t-online.de
Draenert
R
R
Dusel
G
G
Richter
F
F
Liebscher
E
E
Christl
S U
SU
Scheppach
W
W
Kasper
H
H
D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics; D012809:Colon, Sigmoid / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000517:prevention & control*; D003840:Deoxycholic Acid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018038:Sodium Selenite / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D002756:Cholagogues and Choleretics; D003840:Deoxycholic Acid; D018038:Sodium Selenite