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Inhibition of Human Colonic Epithelial Cell Proliferation in Vivo and in Vitro by Calcium¹

Laboratory of Gastrointestinal Cancer Research and Gastroenterology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Nine patients at high risk of developing colon cancer were placed on daily p.o. supplementation of 1500 mg of calcium for 4–8 weeks. The colonic epithelial cells in six of these patients showed a statistically significant decrease in their [³H]thymidine labeling indices in tissue culture so that they resembled those of patients at low risk of developing colon cancer. The three nonresponders had similar labeling indices before and after calcium supplementation. Biopsies from each of nine high-risk patients exhibited a decrease in proliferation when they were cultured in vitro with a high level of CaCl₂ (2.2 mM compared with the 0.1 mM optimum value for proliferation). Two adenomas and two carcinomas showed a different pattern of response than normal cells, exhibiting no inhibition of growth at 2.2 mM CaCl₂. These data indicate that the growth inhibition induced by high levels of extracellular calcium levels is lost at a stage in tumor development before cells become malignant.

¹ Supported by National Cancer Institute Grant 28822 from the National Large Bowel Cancer Project to E. F., National Cancer Institute Grant 40876 and American Cancer Society Grant SIG-7 to M. L., Institutional Grant CA 08748, and grants from the Fondation Rose et Jean Hoguet, Brussels, Belgium, and the North Atlantic Treaty Organization to M. B.

² To whom requests for reprints should be addressed.

Received 3/ 4/86. Revised 7/ 1/86. Accepted 7/ 3/86.

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