The circadian clock regulates cisplatin-induced toxicity and tumor regression in melanoma mouse and human models.

ABSTRACT: Cisplatin is one of the most commonly used chemotherapeutic drugs; however, toxicity and tumor resistance limit its use. Studies using murine models and human subjects have shown that the time of day of cisplatin treatment influences renal and blood toxicities. We hypothesized that the mechanisms responsible for these outcomes are driven by the circadian clock. We conducted experiments using wild-type and circadian disrupted Per1/2^-/- mice treated with cisplatin at selected morning (AM) and evening (PM) times. Wild-type mice treated in the evening showed an enhanced rate of removal of cisplatin-DNA adducts and less toxicity than the morning-treated mice. This temporal variation in toxicity was lost in the Per1/2^-/- clock-disrupted mice, suggesting that the time-of-day

SUBMITTER: Dakup PP 

PROVIDER: S-EPMC5865687 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature