© 1989 Oxford University Press
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SHORT COMMUNICATION: Comparison of 5-bromo-2-deoxyuridine and [3H]thymidine for studies of hepatocellular proliferation in rodents
1Departments of Biochemical Toxicology, Lilly Research Laboratories Eli Lilly and Company, Greenfield, IN 46140, USA
2Departments of Pathology, Lilly Research Laboratories Eli Lilly and Company, Greenfield, IN 46140, USA
3To whom correspondence should be addressed
Hepatocyte replication traditionally has been studied by [3H]thymidine (TdR) incorporation into DNA, and more recently using incorporation of 5-bromo-2-deoxyuridine (BUdR), a synthetic analog of thymidine which is measured by immunohistochemistry. In studies to compare TdR and BUdR, mice were given the peroxisome proliferator [4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14643) in the diet (0.1%) for 5 days and either TdR (1µg) or BUdR (100 mg/kg) on days 25. The labeling index (LI) for hepatocytes of WY-14643-treated mice was 4.7% with BUdR and 5.2% with TdR. The LI for control mice was 0.30.4% with either label. Partially hepatectomized rats given TdR had a mean LI of 30.0 versus 32.0% in rats labeled with BUdR. Sham-operated controls given TdR had a mean LI of 0.2% and BUdR controls had a mean LI of 0.1%. Hepatectomized rats given TdR and BUdR simultaneously had an LI of 20.1% for TdR and 22.4% for BUdR. In these rats, 94.1% of the labeled cells contained both markers, whereas 1.9% had only TdR and 4.0% had only BUdR. Comparable labeling indices using either TdR or BUdR indicate that the analogs may be used interchangeably in short-term in vivo studies of liver cell proliferation.
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