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., methotrexate (MTX), cyclophosphamide (CPA), and ftoral, a derivative of 5-fluorouracil (5-FU), on the gastric, liver, and small-intestine cells of C57B1 mice was studied by transmission electron microscopy. Although no ultrastructural alterations could be detected in the cells of the first two organs, the epithelial cells of the small intestine showed a marked increase in size of their mitochondria. In the control animals the mitochondrial size was in the range of 0.04-1.8 micron (mean +/- SE 0.54 +/- 0.01 micron). In the treated animals the size of the mitochondria ranged between 0.15 and 4.33 micron (mean +/- SE 0.73 micron) for those treated with MTX, 0.24-2.88 micron (mean +/- SE 0.80 +/- 0.02 micron) for those given CPA, and 0.28-5.3 micron (mean +/- SE 1.18 +/- 0.48 micron) 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 long, winding channels of smooth endoplasmic reticulum, vacuoles, and myelin figures. Fluid retention in the small intestine due to administration of cytotoxic drugs is suggested as a possible mechanism for distention of the mitochondria.