In vivo measurements of the proliferation kinetics of epithelial cells in human adenomas were made following i.v. pulse injection of tritiated thymidine ([3H]dThd), in a patient with familial polyposis and Gardner syndrome. In the adenomas and in adjacent flat mucosa, biopsies were taken and microautoradiographs were prepared at intervals after injection. Rates of epithelial cell proliferation, locations of proliferating cells within the crypts of adenomas and adjacent flat mucosa, fractions of [3H]dThd-labeled mitoses and cells, and grain densities were analyzed. Results demonstrated a complete temporal cycle of proliferation of epithelial cells both in adenomas and in flat mucosa, with cells completing only a single cycle during 4 days of observation. Durations of G2 and S phases of the cell cycle were approximately 5 and 15 hr, respectively, both in adenomas and in flat mucosa. After pulse injection, the locations of [3H]dThd-labeled epithelial cells within the adenomatous crypts revealed maximum proliferation near the lumenal surface; proliferation of labeled epithelial cells in flat mucosa occurred in the lower portion of the colonie crypts. The locations of [3H]-dThd-labeled epithelial cells at intervals after injection revealed migration rates of 0.4 cell position/hr in crypts of adenomas and 0.3 cell position/hr in crypts of adjacent flat mucosa. However, in contrast to the migration of epithelial cells toward the lumenal surface of the crypts in flat mucosa, in adenomas a markedly abnormal retrograde average migration away from the surface of the mucosa appeared to occur. This retrograde migration was accompanied by an intrusion of the cells into the adenomatous crypt space, contributing to the infolding which accompanies the expanding epithelium inducing the growth of the adenomas.


Supported in part by American Cancer Society Grant SIG-7 and National Cancer Institute Grant 08748.

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