Circadian clock genes regulate 10-15% of the transcriptome, and might function 
as tumor suppressor genes. Relatively little is known about the circadian clock 
in tumors and its effect on surrounding healthy tissues. Therefore, we compared 
the 24-hr expression levels of key circadian clock genes in liver and kidney of 
healthy control mice with those of mice bearing C26 colorectal tumor metastases 
in the liver. Metastases were induced by injection of C26 colorectal carcinoma 
cells into the spleen. Subsequently, tumor, liver and kidney tissue was 
collected around the clock to compare circadian rhythmicity. Expression levels 
of five clock genes (Rev-Erbα, Per1, Per2, Bmal1 and Cry1) and three 
clock-controlled genes (CCGs; Dbp, p21 and Wee1) were determined by qRT-PCR. 
Liver and kidney tissue of healthy control mice showed normal 24-hr oscillations 
of all clock genes and CCGs, consistent with normal circadian rhythmicity. In 
colorectal liver metastases, however, 24-hr oscillations were completely absent 
for all clock genes and CCGs except Cry1. Liver and kidney tissue of 
tumor-bearing mice showed a shift in clock periodicity relative to control mice. 
In the liver we observed a phase advance, whereas in the kidney the phase was 
delayed. These data show that hepatic metastases of C26 colon carcinoma with a 
disrupted circadian rhythm phase shift liver and kidney tissue clocks, which 
strongly suggests a systemic effect on peripheral clocks. The possibility that 
tumors may modify peripheral clocks to escape from ordinary circadian rhythms 
and in this way contribute to fatigue and sleep disorders in cancer patients is 
discussed.