Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/1/2007
Publication Date: 11/1/2007
Citation: Shih, P., Liu, K., Wells, L., Khalaf, T., Fu, L. 2007. Study of the circadian rhythm in radiation response [abstract]. 5th Annual Cancer Center Symposium p. 82 Interpretive Summary:
Technical Abstract: Gamma-Radiation is often used for the treatment of solid tumors. It induces DNA double-stranded breaks that lead to cell cycle arrest or apoptosis of tumor cells. However, such treatment could also damage normal host tissues that need cell proliferation for function. We have reported previously that the radiation response in peripheral tissues follows the circadian rhythm in vivo. Thus, it is possible to improve therapeutic index by applying radiation at the time when the host tissues are less sensitive to the treatment. The circadian rhythms are generated by an endogenous circadian clock that is operated by the circadian genes. We found previously that the circadian genes not only operate the molecular clock but also control the expression of DNA-damage responsive genes, and mutation in the circadian gene Period2 (Per2) results in an increased radiation-induced tumor development in mice. Here we report that all core circadian gene-mutant mouse models studied show increased tumor development after radiation treatment and that the circadian genes respond to gamma-radiation in a time-dependent manner in peripheral tissues during a 24-hr period. Thus, the molecular clock is potentiated differently during the 24- hr period in response to gamma-radiation. We hypothesize that such time-dependent clock activation controls the circadian rhythm in radiation response in vivo. To test this hypothesis, we first studied the transcription control of Per2, and identified a Per2 promoter sequence responsible for Per2 induction following gamma-radiation. Future studies will be focused on identifying the factors interacting with this sequence and whether, as well as, how the interactions are differentially controlled during the 24-hr period in vivo. These studies will reveal how the circadian rhythm in radiation response is controlled in vivo.