Transgene expression of thioredoxin (TRX/ADF) protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hematotoxicity
| Autor: | Junji Yodoi, Tohru Inoue, T. Kaneko, Dae Yong Kim, Yoko Hirabayashi, B.I. Yoon, Yukio Kodama, Jun Kanno |
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| Rok vydání: | 2000 |
| Předmět: |
Polychlorinated Dibenzodioxins
Health Toxicology and Mutagenesis Transgene medicine.medical_treatment Hematopoietic System Intraperitoneal injection Bone Marrow Cells Mice Transgenic Biology Toxicology medicine.disease_cause Mice Thioredoxins Western blot Bone Marrow medicine Animals heterocyclic compounds Transgenes chemistry.chemical_classification Reactive oxygen species medicine.diagnostic_test General Medicine Pollution Molecular biology Haematopoiesis Oxidative Stress medicine.anatomical_structure chemistry Gene Expression Regulation Immunology Environmental Pollutants Bone marrow Thioredoxin Oxidative stress |
| Zdroj: | Archives of environmental contamination and toxicology. 41(2) |
| ISSN: | 0090-4341 |
| Popis: | TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has a variety of toxic effects on a number of organs, including the hematopoietic system. The importance of TCDD-induced oxidative stress has been evaluated in several target organs. However, its role in hematotoxicity remains poorly understood, although bone marrow is known to produce reactive oxygen species. The aim of this study is to evaluate not only the contribution of oxidative stress to TCDD-induced hematotoxicity but also the protective function of TRX/ADF, a known anti-oxidative stress agent, on the hematotoxicity of TCDD in ADF wild-type (WT) and transgenic (Tg) mice. WT and Tg mice received a single intraperitoneal injection of 20 microg TCDD/kg. One day after the treatment, blood and bone marrow cellularity was measured and bone marrow levels of granulotyce/macrophage colony-forming units were determined in the in vitro colony assay. The expression of human TRX transgene by their bone marrow cells was analyzed by Western blot electrophoresis. Our results showed that overexpression of TRX/ADF protects against TCDD-induced hematotoxicity, indicating that induction of oxidative stress that results in disruption of redox regulation may be an important mechanism in TCDD-induced bone marrow toxicity. Moreover, we detected a significant decrease of AhR mRNA levels in bone marrow cells of Tg mice following TCDD treatment, suggesting a biological role of TRX/ADF in the AhR-mediated pathway through which TCDD induces oxidative stress. |
| Databáze: | OpenAIRE |
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