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UNC study supports role of circadian clock in response to chemotherapy
Date:1/13/2009

cillatory behavior is the circadian clock, which keeps the biochemical, behavioral and physiological processes of many organisms, including mice and humans, on a 24-hour cycle. Every single cell in the body whether from the kidney, liver or heart has its own internal clock, and each of these are synchronized and coordinated by one master clock, located in a particular cluster of neurons in the brain.

Because of the important role that the circadian clock plays in regulating the daily rhythms of life, Sancar wanted to see what influence it had on important functions in the body, in particular the repair of damage to DNA caused by chemotherapy or UV radiation. This damage is usually repaired by a process called nucleotide excision repair, which cuts out and replaces sections of damaged DNA.

Sancar and his colleagues studied the behavior of the repair machinery in cerebrum or brain tissue of mice over the course of a day, and found that the ability to repair damage was at a minimum in the early morning and reached a maximum in the evening hours. They then looked at each of the six components that make up the repair machinery and found that the levels of one of them the enzyme XPA rose and fell in synchrony with the oscillations of the circadian clock. Thus, the researchers demonstrated that the cell's ability to repair damage is linked to the circadian clock, and that this daily oscillation is ultimately due to changes in the levels of one particular enzyme at different times of day.

Sancar now wants to extend these studies to determine whether the same cyclical changes in repair activity seen in mouse brain can also be observed in mouse testis. This avenue is particularly relevant because cisplatin a chemotherapeutic agent commonly used to treat testicular cancer kills cancer cells by damaging DNA.

While cisplatin is considered by many people to be a miracle drug it completely cured Lance Armstrong one in ten patients wh
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Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert

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