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 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 (1 microCi/g) or BUdR (100 mg/kg) on days 2-5. 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 0.3-0.4% 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.
Lanier
T L
TL
Department of Biochemical Toxicology, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN 46140.
Berger
E K
EK
Eacho
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PI
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication; D005260:Female; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008830:Microbodies / Q000187:drug effects / Q000648:ultrastructure; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D013936:Thymidine / Q000378:metabolism*; D014316:Tritium
D011743:Pyrimidines; D014316:Tritium; C006253:pirinixic acid; D001973:Bromodeoxyuridine; D013936:Thymidine