Colonic epithelial cell proliferation in responders and nonresponders to supplemental dietary calcium.

Supplemental dietary calcium decreased and normalized hyperproliferation of colonic epithelial cells in individuals in familial colon cancer kindreds, measured by rates and patterns of [3H]thymidine labeling of epithelial cells in colonic crypts. In whole colonic crypts hyperproliferation was decreased to lower levels in over one-half of the subjects individually studied during the course of the calcium supplementation regimen. The remaining familial colon cancer subjects did not show reductions in cell proliferation measured over the whole crypt. However, when their cell-labeling data were analyzed in regions of the colonic crypt, the size of the proliferative compartment decreased and contracted towards the crypt base after calcium, a pattern typical of individuals at decreased risk for colonic cancer. This contraction of the proliferative region of the crypts occurred through decreased cell labeling in the two crypt compartments closest to the luminal surface and increased cell labeling in the second crypt compartment nearest to the base of the crypt. Following in vitro exposure of colonic epithelial cells to increasing physiological amounts of calcium, cell proliferation in familial colon cancer subjects decreased uniformly and greater heterogeneity in responsiveness was observed in cells from individuals with familial polyposis.