Circadian rhythm and 5-fluorouracil toxicity in C3H mice.

In order to study the effect of daily (circadian) rhythm on toxicity of an anticancer drug, 5-fluorouracil, adult female C3H mice were used in this work. A dose of 200 mg/kg of 5-FU was administered intraperitoneally to the animals. Body weights and animal mortality were observed daily during the following 21 days after administration of the drug. The most severe toxic effect of 5-FU, with 100% mortality, was observed when the drug was administered at 4 am, whereas at 12 am 5-FU was least toxic. Since C3H mice are nocturnal animals, they are at the peak activity in the early morning hours of the day. Thus, it seems that an increased 5-FU toxicity in C3H mice coincides with an increased metabolic rate and other physiological processes of these nocturnal animals.