DNA synthesis and telomerase activity were assessed in nude mice transplanted with hepatic carcinoma. Hepatic cancer cells (SMMC-7721) were implanted into both flanks of each of 14 BALB/C mice synchronized in 12h of light alternating with 12h of darkness (LD12:12) for 4 weeks. At 7 timepoints, tumor samples were collected for measurement of cellular DNA content by flow cytometry and telomerase activity by PCR-ELISA assay. Cosinor analyses determine a 24-h rhythm for all variables, showing a similar timing for the DNA-synthesis phase and telomerase activity. These results provide a model for exploring optimal timing of chronotherapy with peptides, especially for treatment with telomerase inhibitors.
Bibliographical noteFunding Information:
National Nature Science Foundation of China (project 39970275, 30070198 for W.Z. and W.C.); U.S. Public Health Service (GM-13981) (F.H.); Dr. h.c. Earl Bakken Fund (G.C., F.H.); University of Minnesota Supercomputing Institute (G.C., F.H.).
- Cell cycle
- Circadian rhythm
- DNA synthesis
- Hepatic carcinoma
- Nude mice
- Telomerase activity