Apoptosis in normal tissues induced by 5-fluorouracil: comparison between bolus injection and prolonged infusion.

The induction of apoptosis in normal tissues was histopathologically examined in rats treated with 5-fluorouracil (5-FU). 5-FU was administered by either bolus intravenous injection or 72-hr prolonged intravenous infusion (PIF). Bolus injection and PIF of 5-FU induced different kinetic profiles of apoptosis in the thymus, spleen and ileum. The bolus injections of 5-FU induced a greater extent of apoptosis in these tissues, compared to PIF 5-FU. These data indicate that the kinetics and extent of apoptosis induced by 5-FU depends on the schedule of the 5-FU administration, and that 5-FU-induced toxicity may be related to 5-FU-induced apoptosis in normal tissues.