An In Vivo Method for Using 5-Bromo-2'-deoxyuridine (BrdU) as a Marker of Chemically-Induced Hepatocellular Proliferation in the Japanese Medaka (Oryzias latipes)
| Autor: | E. Maxine Boncavage-Hennessey, William E. Dennis, Alan B. Rosencrance, Marilyn J. Wolfe, Henry S. Gardner, Linda M. Brennan, Margaret W. Toussaint |
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| Rok vydání: | 2001 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Time Factors Carcinogenicity Tests Oryzias Toxicology medicine.disease_cause Adenoma Liver Cell S Phase Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound In vivo Biomarkers Tumor medicine Animals Diethylnitrosamine Molecular Biology Dose-Response Relationship Drug 030102 biochemistry & molecular biology biology Cell growth Liver Neoplasms Cell Biology Japanese Medaka Anatomy biology.organism_classification Molecular biology digestive system diseases Deoxyuridine Disease Models Animal Dose–response relationship 030104 developmental biology Bromodeoxyuridine Liver chemistry Carcinogens Hepatocytes Immunohistochemistry Carcinogenesis Cell Division |
| Zdroj: | Toxicologic Pathology. 29:387-397 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1080/019262301316905354 |
| Popis: | Japanese medaka fish ( Oryzias latipes) were used to develop an in vivo method to assess hepatocellular proliferation in a nonmammalian model. Proliferative responses were assessed in medaka at 7, 17, 24, and 94 days after a 48-hour exposure to 10 or 100 mg/L diethylnitrosamine (DEN). Subgroups of medaka were exposed to 50 or 75 mg/L of 5-bromo-2'-deoxyuridine (BrdU) in water for 72 hours, sacrificed, and then processed for immunohistochemical staining. Proliferative indices of BrdU-labeled hepatocytes were quantified and compared using both count and area measurements. There was a significant increase ( p < 0.05) in hepatocellular proliferation in the 100 mg/L DEN-treated fish as compared to controls and 10 mg/L DEN-treated fish for the first 3 time points. Hepatocarcinogenicit y was evaluated 26 weeks post-DEN exposure. There was a significant increase ( p < 0.0001) in hepatocellular neoplasms in 100 mg/L DEN-treated fish compared to other fish. Effective BrdU-labeling of S-phase hepatocytes in medaka was achieved by adding BrdU to the aquarium water, and an increase in hepatocellular proliferation using this method was detected 7 days after exposure to a carcinogenic concentration of DEN. Additionally, the new method of area measurement indices of proliferation were as precise as count indices (R2≥0.92). |
| Databáze: | OpenAIRE |
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