Changes in the mucosa of the small intestine following methotrexate administration or abdominal X‐irradiation

Abstract

Abstract Adult male rats received 5 mg methotrexate daily and were sacrificed 1, 1.5, 2, 2.5 and 3 days after the beginning of the treatment. Other groups received 9,000 rads of abdominal x‐radiation and were sacrificed 1, 2 and 3 days later. Histological samples were taken from five regions of the small intestine and processed for light microscopic examination. Average area occupied by the crypts and the villi respectively, was measured per unit length of histological section. A few animals received 3 H‐thymidine an hour before the methotrexate treatment or irradiation; the histological samples were processed for radioautography. Significant mitotic activity was absent throughout the experiments. During the first 1.5 days, mainly the crypts diminished. Radioautography revealed that migration of crypt cells to the villi continued during this time. During the second and third days, the villi also showed marked diminution, and cell migration became irregular. In general, the histometric data were similar after methotrexate and irradiation. Epithelial denudation started in terminal ileum on the third day after methotrexate. The epithelium was much reduced but not yet denuding at this time in the irradiated animals. Methotrexate inhibition of DNA and RNA synthesis was assumed to be associated, respectively, with mitotic inhibition and with a decline of protein synthesis which manifested itself in villus diminution. Survival of epithelial cells varied presumably according to the amount of RNA pool and was longest in cells being in the S‐phase at the onset of the treatment. The similarity of the data after irradiation implied a similar sequence of events.