Key result
Thymidylate synthase activity varies up to 2-fold throughout the day in normal tissues most damaged by fluoropyrimidines, paralleling the circadian rhythm in cellular proliferation.
Population
Female mice living on a 12:12 hr light:dark schedule
Comparison
Harvesting normal tissues at 6 different… vs Different times of the day
Design
Preclinical
Authors
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Supports timing fluoropyrimidine dosing to minimize normal-tissue TS activity; leaves open clinical benefit of chronotherapy in patients.
Effect estimate: up to 2-fold variation throughout the day
Circadian variation in thymidylate synthase activity in normal tissues may explain the time-of-day differences in the toxic-therapeutic ratio of fluoropyrimidine chemotherapy.
Lincoln et al. (2000) studied Circadian rhythm of thymidylate synthase activity. Time of day (circadian timing) vs. Different times of day was evaluated on Thymidylate synthase (TS) catalytic activity (up to 2-fold variation throughout the day). Thymidylate synthase activity varies up to 2-fold throughout the day in normal tissues most damaged by fluoropyrimidines, paralleling the circadian rhythm in cellular proliferation.
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