SHORT COMMUNICATION: Comparison of 5-bromo-2-deoxyuridine and [3H]thymidine for studies of hepatocellular proliferation in rodents

Hepatocyte replication traditionally has been studied by [³H]thymidine(TdR) incorporation into DNA, and more recently using incorporationof 5-bromo-2-deoxyuridine (BUdR), a synthetic analog of thymidinewhich is measured by immunohistochemistry. In studies to compareTdR and BUdR, mice were given the peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14643) in thediet (0.1%) for 5 days and either TdR (1µg) or BUdR (100mg/kg) on days 2–5. The labeling index (LI) for hepatocytesof WY-14643-treated mice was 4.7% with BUdR and 5.2% with TdR.The LI for control mice was 0.3–0.4% with either label.Partially hepatectomized rats given TdR had a mean LI of 30.0versus 32.0% in rats labeled with BUdR. Sham-operated controlsgiven TdR had a mean LI of 0.2% and BUdR controls had a meanLI of 0.1%. Hepatectomized rats given TdR and BUdR simultaneouslyhad 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 indicesusing either TdR or BUdR indicate that the analogs may be usedinterchangeably in short-term in vivo studies of liver cellproliferation.