Light and scanning electron microscopic observations of the effects of sublethal doses of methotrexate on the rat small intestine.

The small intestines of adult rats were examined by light and scanning-electron microscopy after sublethal doses of methotrexate were injected at 5, 3 and 1 mg, respectively, per rat per day, for three days. Methotrexate inhibited mitosis and thereby disrupted the steady state system of the epithelium. Villi and crypts progressively diminished up to about four and one-half days after the initial injection. Thereafter, recovery began and, by day 7, relatively normal morphology was restored. In the degenerative phase, the loss of crypt-villus continuum was frequently observed, the former crypts forming cyst-like structures. The columnar cells became flat and pleomorphic but epithelial continuity was maintained. Goblet cells apparently decreased in number. Paneth cells, especially in the ileum, appreciably increased in size and number. During the recovery phase, the cystic crypts apparently re-established continuity with the villus epithelium. Size and proportion of all epithelial cell types returned to normal. Scanning electron microscopy showed villus fusion and the cellular pleomorphism and loss of microvilli during the degenerative phase. During recovery of the villi some alteration in orientation and shape remained as shown by scanning electron microscopy.