2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) or Diethylstilbestrol (DES) Cause Similar Hematopoietic Hypocellularity and Hepatocellular Changes in Murine Fetal Liver, but Differentially Affect Gene Expression
| Autor: | Kurt L. Zimmerman, Elizabeth G. Besteman, Steven D. Holladay, William R. Huckle, M. Renee Prater, Robert M. Gogal |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Polychlorinated Dibenzodioxins Protein Kinase C-alpha 040301 veterinary sciences medicine.drug_class Diethylstilbestrol Biology Toxicology 030226 pharmacology & pharmacy Pathology and Forensic Medicine 0403 veterinary science Mice 03 medical and health sciences Fetus 0302 clinical medicine Genes jun Megakaryocyte Pregnancy Internal medicine Gene expression medicine Animals RNA Messenger Molecular Biology 04 agricultural and veterinary sciences Cell Biology Genes p53 Hematopoietic Stem Cells medicine.disease Mice Inbred C57BL Endocrinology medicine.anatomical_structure Hypocellularity Basophilia Liver Estrogen Toxicity Female medicine.drug |
| Zdroj: | Toxicologic Pathology. 35:786-792 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | TCDD and DES have immunotoxic effects, including selective diminution of T lymphocyte progenitors in the fetal liver. The histologic presentation of fetal liver after exposure to either chemical has not been described. Similarly, limited information exists regarding mechanisms by which TCDD or DES may alter fetal hematopoiesis. Treatment of pregnant C57BL/6 mice with either 10 μg/kg/day TCDD or 48 μg/kg/day DES on gestation days (gd) 14 and 16 led to increased fetal liver weight on gd 18. Moderate anisocytosis and anisokaryosis with increased cytoplasmic and nuclear sizes, and increased cytoplasmic basophilia were present within hepatocytes after TCDD or DES. Both chemicals also decreased the presence of hematopoietic cells, however megakaryocyte numbers were unaffected. In contrast to these similar outcomes, real time quantitative PCR using a preliminary panel of 4 genes suggested that the chemicals act through different gene targets. TCDD increased c-jun gene expression in fetal liver, and decreased p53 without alteration in bcl-2 expression, indicating possible pro-proliferative and antiapoptotic effects. DES decreased c-jun and bcl-2, without altering p53, suggesting a shift away from proliferation. Both agents decreased PKC α expression, which may suggest shared decreased phosphorylation of substrates required for normal cell cycle progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|