The differential effects of two salts of 5-fluorouracil and of dietary restriction on absorption by rat small intestine

Water absorption, measured in vitro in the perfused rat small intestine, following injection of the Tris or sodium salt of 5-fluorouracil (5FU) has been compared with that following a food restriction regime which mimicked the food intake pattern of rats after injection of 5FU. Water absorption rates were decreased both after administration of 5FU and after food restriction but the decrease following 5FU injection was much greater. Also, the Tris and sodium salts of 5FU had different effects on the food intake pattern after injection but had very similar effects on intestinal absorption of water. Hence the effects of 5FU on absorption cannot wholly be attributed to a reduced food intake. Four reference systems have been used to express water absorption rates: whole small intestine, unit length of intestine, intestinal dry weight and mucosal DNA content. The importance of the choice of reference system is discussed. Due to the heterogeneity of the mucosal cell population the use of DNA and dry weight as reference systems could not give an unequivocal indication of whether the changes in absorption rates resulted from a change in the number of absorbing cells or from a change in the absorptive capacity of each absorbing cell. Severe systemic toxicity, including death, was observed after injection of the Tris salt of 5FU, but not after injection of the sodium salt.