Diurnal variation in the intestinal toxicity of 5-fluorouracil in the rat.
1. Water absorption rates by small intestine in vitro and the incidence of diarrhoea in vivo were estimated after 5-fluorouracil was injected into rats at various times of day and night. 2. Impairment of water absorption and the incidence of diarrhoea were minimal in rats on a normal dietary regimen when the 5-fluorouracil was injected at around 02.00 hours. 3. The DNA content of the mucosa of the small intestine from uninjected animals also showed a diurnal variation, with a maximum at around 03.00 hours. 4. Manipulation of the time of injections (possibly in relation to feeding time) provides a potential means for increasing the therapeutic value of 5-fluorouracil.
D000818:Animals; D002940:Circadian Rhythm; D004247:DNA / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced; D005472:Fluorouracil / Q000633:toxicity*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014867:Water / Q000378:metabolism
D014867:Water; D004247:DNA; D005472:Fluorouracil