論文 - 詳細
| RRC ID | 36427 |
|---|---|
| 著者 | Tu TY, Hong CY, Sasado T, Kashiwada S, Chen PJ. |
| タイトル | Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish. |
| ジャーナル | Aquat Toxicol |
| Abstract |
Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53(-/-) mutant of medaka fish (Oryzias latipes) to propiconazole (2.5-250μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53(-/-) mutant medaka with early life exposure to propiconazole showed increased incidence of hepatocarcionogensis, as compared to the p53(-/-) control group and wild type strain. We demonstrated that propiconazole can initiate ROS-mediated oxidative stress and induce hepatic tumorigenesis associated with CYP1A- and/or p53 -mediated pathways with the use of wild type and p53(-/-) mutant of medaka fish. The toxic response of medaka to propiconazole is compatible with that observed in rodents. |
| 巻・号 | 170 |
| ページ | 52-61 |
| 公開日 | 2016-1-1 |
| DOI | 10.1016/j.aquatox.2015.11.014 |
| PII | S0166-445X(15)30095-3 |
| PMID | 26619215 |
| MeSH | Animals Antioxidants / metabolism Biomarkers / metabolism Carcinogens / toxicity* Catalase / metabolism Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism Environmental Exposure / analysis* Fungicides, Industrial / toxicity* Gene Expression Regulation / drug effects Glutathione Transferase / metabolism Larva / drug effects Larva / metabolism Lipid Peroxidation / drug effects Liver / drug effects Liver / metabolism Liver / pathology Liver Neoplasms / etiology* Liver Neoplasms / genetics Liver Neoplasms / pathology Macrophages / drug effects Macrophages / metabolism Oryzias / growth & development Oryzias / metabolism* Oxidative Stress / drug effects* Reactive Oxygen Species / metabolism Superoxide Dismutase / metabolism Time Factors Transcription, Genetic / drug effects Triazoles / toxicity* Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism Water Pollutants, Chemical / toxicity |
| IF | 4.346 |
| 引用数 | 16 |
| WOS 分野 | MARINE & FRESHWATER BIOLOGY TOXICOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| メダカ | p53(E241x) MT894 |