In studies of cell proliferation in the intestine of animals during the past few years, observations have been made that suggest points of interest concerning cell renewal in humans. In rodents, proliferating jejunal and colonic epithelial cells have mean generation times of about 12 to 18 hours, DNA synthesis (S phase) times of 5 to 8 hours, and premitosis (G2) and mitosis (M) times of 1 to 2 hours (1-3). Also, although many epithelial cells undergo a second generation cycle soon after mitosis, some cells appear to remain longer in interphase before dividing again (3). The rate of disappearance of labeled cells from the mucosa has also been shown to vary in different portions of the gastrointestinal tract in a number of species; e.g., more labeled cells are present in the colon and stomach 1 week after injection of H3-thymidine than in the duodenum or jejunum (4).In man, studies of mitotic indexes and radioautographic studies with H3-thymidine have suggested turnover times of intestinal epithelial cells in the order of several days (5-7). In the present study, we have measured the mean generation time and the phases of the proliferative cycle of human colonic and rectal epithelial cells after the administration of H3-thymidine. The results describe cell renewal and give data on the rate of disappearance of labeled cells from the mucosa of the human colon and rectum.
METHODSTwo patients with colostomies were studied. Both had resections of the descending colon for carcinoma of the rectum and liver metastases. The colostomies were composed of normal mucosa of the transverse colon. A * Supported in part by U. S. Public Health Service grants A-3165 and C-3697, and by The John A. Hartford Foundation, Inc., New York, N. Y. third patient with a carcinoma of the rectum 8 cm proximal to the anal orifice was studied. Although all patients had carcinoma and known metastases, and had recently lost weight, they were fairly well-nourished at the time of these studies. Figure 1. The zone of rapid epithelial cell proliferation is located in the lower and middle third of the colonic crypts. In Figure 1A, labeled proliferating cells are seen blended 767
Department, Pittsburgh, Pa, in which S.K. and her mother were treated. We also express our thanks to Ellen Wald, MD, for her critical reading of the manuscript, and the Children's Hospital of Pittsburgh Cardiothoracic Trans¬ plant Team for their analytical discussion of the issues.1. Kantrowitz A, Haller JD, Joos H, Cerruti MM, Carstensen HE. Transplantation of the heart in an infant and an adult. Am J Cardiol. 1968;22:782-790.
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