EFFECT OF ORAL CHEMOTHERAPY ON THE MITOCHONDRIAL SIZE OF MOUSE INTESTINAL-CELLS

Since orally given cytotoxic agents may cause intestinal disfunction, the effect of oral administration of three cytotoxics, i.e., methotrex ate (MTX), cyclo-phosphamide (CPA), and ftoral, a derivative of 5-fluo rouracil (5-FU), on the gastric, liver, and small-intestine cells of C 57B1 mice was studied by transmission electron microscopy. Although no ultrastructural alterations could be detected in the cells of the fir st two organs, the epithelial cells of the small intestine showed a ma rked increase in size of their mitochondria. In the control animals th e mitochondrial size was in the range of 0.04-1.8 mu m (mean +/- SE 0. 54 +/- 0.01 mu m). In the treated animals the size of the mitochondria ranged between 0.15 and 4.33 mu m (mean +/- SE 0.73 mu m) for those t reated with MTX, 0.24-2.88 mu m (mean +/- SE 0.80 +/- 0.02 mu m) for t hose given CPA, and 0.28-5.3 mu m (mean +/- SE 1.18 +/- 0.48 mu m) for those treated with 5-FU. These findings were significantly different from those obtained in controls (P < 0.0001). In addition, in animals treated with MTX the mitochondria of the jejunal cells were surrounded by channels of rough endoplasmic reticulum. The cytoplasm contained l ong, winding channels of smooth endoplasmic reticulum, vacuoles, and m yelin figures. Fluid retention in the small intestine due to administr ation of cytotoxic drugs is suggested as a possible mechanism for dist ention of the mitochondria.