Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances

Treatment with 5-fluorouracil (5-FU) significantly reduced mRNA levels of Period1 (Per1) and Period2 (Per2) in cultured cells.

• 5-FU, a common chemotherapeutic agent, is associated with disturbances in circadian rhythms and behavioral performance in patients.
• Cultured NIH3T3 cells exposed to 5-FU for 48 hours showed significant decreases in Per1 and Per2 expression without loss of cell viability.
• Uracil, a structural analog of 5-FU, had minimal impact on the expression of clock genes.
• In mice, continuous administration of 5-FU led to reduced oscillation of Per1 and Per2 expression in both the liver and the suprachiasmatic nuclei.
• These findings suggest that 5-FU may influence the circadian clock mechanism, potentially contributing to its adverse effects.

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