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   <subfield code="a">Production of liver preneoplasia and gallbladder agenesis in turkey fetuses administered diethylnitrosamine</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[Gary Williams, Klaus Brunnemann, Michael Iatropoulos, Daniel Smart, Harald Enzmann]</subfield>
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   <subfield code="a">The in ovo carcinogenicity assessing (IOCA) assay was used to examine the morphological changes in fetal turkey livers caused by the DNA-reactive carcinogen diethylnitrosamine (DEN). Fertilized turkey eggs were allocated into 3 groups: nondosed control (NDC), vehicle (water) control (VC) and DEN-dosed. At day 0, the fertilized eggs of the dosed groups were injected with 1 (LD) or 4 (HD) mg/egg (about 12.5 or 50 mg/kg egg) of DEN and the VC were injected with water. All eggs were allowed to incubate at 37°C and 60% humidity for 24days. The fetal livers were collected and processed for histopathological evaluation (H&amp;E staining). Typical survival rates were 82% for the NDC, 50% for the VC and 16-65% for the DEN-dosed fetuses. No difference in histology was found between NDC and VC control groups. Both DEN concentrations produced dose-related liver findings consisting of foci of altered hepatocytes (FAH), which had assumed a tubular cord (glandular) pattern, and in HD DEN group the FAH assumed a tumor-like morphology. In addition, the high DEN dose produced gallbladder agenesis. Thus, DEN produced both hepatocellular transformation (FAH) similar to preneoplastic microscopic changes in adult rodents, reflecting disruption of the fetal processes of differentiation and proliferation, and also teratogenicity (gallbladder agenesis).</subfield>
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   <subfield code="a">In ovo carcinogenicity assessing assay in turkey</subfield>
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   <subfield code="a">Diethylnitrosamine</subfield>
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   <subfield code="a">Proliferation and preneoplasia</subfield>
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   <subfield code="a">BfArM : Federal Institute for Drugs and Medical Devices of Germany</subfield>
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   <subfield code="a">DEN : Diethylnitrosamine</subfield>
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   <subfield code="a">FAH : Foci of altered hepatocytes</subfield>
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   <subfield code="a">GLP : Good Laboratory Practices for Nonclinical Laboratories</subfield>
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   <subfield code="a">HD : High dose of DEN</subfield>
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   <subfield code="a">H&amp;E : Hematoxylin and eosin stain</subfield>
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   <subfield code="a">IOCA : In ovo carcinogenicity assessing assay</subfield>
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   <subfield code="a">NOAEL : No adverse effect level</subfield>
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