In Situ Detection of Cell Proliferation

Evaluation of cell proliferation in tissues of experimental animals is essential for toxicology and carcinogenesis studies and also to assess the efficiency of cytotoxic and chemopreventive drugs in cancer research. Detection of proliferating cells in tissue sections can be achieved by a number of methods. The gold standard has long been the in vivo labeling of DNA by the modified pyrimidine analogue, a halogenated derivative of thymidine, BrdU. BrdU can be administered to laboratory animals via IP injection for use in pulse-label experiments or via osmotic pumps for use in continuous-label studies. BrdU is readily incorporated into nuclei during the DNA synthetic phase of the cell cycle (S-phase) and is detected by IHC with an anti-BrdU antibody. BrdU IHC has proved useful for identifying S-phase cells. Another IHC technique that has found application in the assessment of cell proliferation is the detection of Ki-67. The antigen Ki-67 is a ubiquitous human nuclear protein expressed in G1-, S-, and G2-phases of the cell cycle but not in the G0-phase and is therefore a measure of the growth fraction. The usefulness of Ki-67 IHC in tumor diagnostics has been well established for various types of malignancies.

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