Autor: |
Brennan, Linda M., Boncavage-Hennessey, E. Maxine, Wolfe, Marilyn J., Toussaint, Margaret W., Dennis, William E., Rosencrance, Alan B., Gardner Jr, Henry S. |
Předmět: |
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Zdroj: |
Toxicologic Pathology; May/Jun2001, Vol. 29 Issue 3, p387-397, 11p, 3 Black and White Photographs |
Abstrakt: |
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. Hepatocarcinogenicity 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 (R[sup 2] ≥ 0.92). [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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