This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verbin, R. S. Articles by Farber, E. Search for Related Content PubMed PubMed Citation Articles by Verbin, R. S. Articles by Farber, E.

The Effects of Cytosine Arabinoside upon Proliferating Epithelial Cells¹

Departments of Pathology, University of Pittsburgh Schools of Medicine and Dental Medicine, Pittsburgh, Pennsylvania 15213

Experiments were conducted to obtain additional insight into the response patterns of the intestinal crypts to 1-ß-D-arabinofuranosylcytosine, a potent inhibitor of DNA synthesis. The results indicate that this interference with nucleic acid metabolism is not lethally toxic to the crypt epithelial cells. This formulation is based on the following observations: (a) the absence of definitive ultrastructural manifestations of irreversible cell damage, particularly with respect to the nucleus; (b) the presence of labeled thymidine in virtually 100% of the mitotic figures occurring during recovery from the inhibitory effects of the analog; (c) the enhanced mitotic activity which closely followed the resumption of a considerable degree of DNA synthesis; (d) the failure to find any indication of intestinal epithelial cell death in animals killed 24 and 48 hr after the first of multiple injections of 1-ß-D-arabinofuranosylcytosine; and (e) the absence of histological evidence of cell death in a number of other epithelial tissues programmed for continuous replication. In contrast, however, stigmata of severe cytotoxic effects were readily discernible in the intestinal lymphocytes. It is therefore concluded that the apparent necrosis of the intestinal crypts noted with conventional microscopy actually represents phagocytosis of degenerating lymphocytic elements by adjacent crypt epithelial cells.

¹ This research was supported in part by Grants CA-11390 and CA-12218 from the National Cancer Institute, Grant AM-14882 from the National Institute of Arthritis and Metabolic Diseases, and Grants IN-581 and BC-7N from the American Cancer Society.

² Recipient of a Career Development Award (5 KO4 DE 35 155) from the National Institute of Dental Research.

³ Present address: Fels Research Institute, Temple University School of Medicine, Philadelphia, Pa. 19140.

Received 12/22/71. Accepted 3/29/72.

This article has been cited by other articles:

				G. Lux, L. Marton, and S. Baylin Ornithine decarboxylase is important in intestinal mucosal maturation and recovery from injury in rats Science, October 10, 1980; 210(4466): 195 - 198. [Abstract] [PDF]