Circadian sensitivity to the chemotherapeutic agent cyclophosphamide depends on the functional status of the CLOCK/BMAL1 transactivation complex.

ABSTRACT: The circadian clock controls many aspects of mammalian physiology, including responses to cancer therapy. We find that wild-type and circadian mutant mice demonstrate striking differences in their response to the anticancer drug cyclophosphamide (CY). While the sensitivity of wild-type mice varies greatly, depending on the time of drug administration, Clock mutant and Bmal1 knockout mice are highly sensitive to treatment at all times tested. On the contrary, mice with loss-of-function mutations in Cryptochrome (Cry1-/-Cry2-/- double knockouts) were more resistant to CY compared with their wild-type littermates. Thus, both time-of-day and allelic-dependent variations in response to chemotherapy correlate with the functional status of the circadian CLOCK/BMAL1 transactivation complex. Pharma

SUBMITTER: Gorbacheva VY 

PROVIDER: S-EPMC546637 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature