OBJECTIVES: The aim of this study was to determine the effects of 96 hour exposure to selected solvents on the embryonic stages of zebrafish (Danio rerio). We investigated mortality and various types of changes which appeared (oedema, tail and eye defects, weak pigmentation, and deformation of the body). Based on the results, values of NOEC and LOEC for embryos of D. rerio were determined. METHODS: Embryonal toxicity tests were conducted according to OECD guideline 212. Ethanol and methanol were tested at concentrations of 0.1, 0.5, 1, 1.5, 2%; acetone at concentrations of 0.1, 0.5, 1, 1.25, 1.5%; and dimethylsulfoxide at concentrations of 1, 1.5, 2, 2.5, 3%. RESULTS: The LOEC values of ethanol and methanol were detected in the 1% concentration. Statistically significant changes (oedema) were reported in 1% ethanol, and oedema, weak pigmentation and deformation of the body were observed in 1% methanol. After exposure to acetone, the most common occurrence of oedema was in the 0.5% concentration (LOEC = 0.5%). The solvent dimethylsulfoxide caused oedema and body deformation at the 2% concentration (LOEC = 2%). CONCLUSIONS: The NOEC concentrations of the individual solvents were as follows: ethanol and methanol, 0.5%; acetone, 0.1%; and dimethylsulfoxide, 1.5%. These concentrations of individual solvents were higher than the maximum recommended concentration for toxicity tests on fish. For this reason, it can be assumed that the concentration of solvent allowed by the norm does not affect the procedure or results of such tests.
- MeSH
- abnormality očí chemicky indukované MeSH
- aceton toxicita MeSH
- dánio pruhované embryologie MeSH
- dimethylsulfoxid toxicita MeSH
- edém chemicky indukované MeSH
- embryo nesavčí účinky léků MeSH
- ethanol toxicita MeSH
- methanol toxicita MeSH
- mnohočetné abnormality chemicky indukované MeSH
- pigmentace kůže účinky léků MeSH
- rozpouštědla toxicita MeSH
- testy toxicity MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
In contrast to hepatocytes, there is only limited information about the expression and activities of enzymes participating in metabolic activation of environmental mutagens, including polycyclic aromatic hydrocarbons (PAHs), in liver progenitor cells. In rat liver "stem-like" WB-F344 cell line, sharing many characteristics with rat liver progenitor cells, PAHs are efficiently activated to their ultimate genotoxic metabolites forming DNA adducts. The present study aimed to characterize expression/activities of enzymes of two major pathways involved in the metabolism of benzo[a]pyrene (BaP): cytochrome P450 (CYP) family 1 enzymes and cytosolic aldo-keto reductases (AKRs). We report here that, apart from induction of CYP1A1 and CYP1B1 expression and the corresponding enzymatic activity, both BaP and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced rat 3alpha-hydroxysteroid dehydrogenase (AKR1C9) expression and activity. In contrast, the aldehyde reductase AKR1A1 was not induced by either treatment. Thus, both CYP1 and AKR metabolic pathways were inducible in the model of liver progenitor cells. BaP and TCDD were efficient inducers of NAD(P)H:quinone oxidoreductase 1 (NQO1) expression and activity in WB-F344 cells, a principal enzyme of cellular antioxidant defense. Both compounds also induced expression of transcription factor NRF2, involved in control of enzymes protecting cells from oxidative stress. However, although BaP induced a significant formation of reactive oxygen species, it did not induce expression of heme oxygenase-1, suggesting that induction of oxidative stress by BaP was limited. Using shRNA against the aryl hydrocarbon receptor (AhR), we found that similar to CYP1A1 and CYP1B1, the AKR1C9 induction was AhR-dependent. Moreover, constitutive AKR1C9 levels in AhR-deficient rat BP8 hepatoma cells were significantly lower than in their AhR-positive 5L variant, thus supporting possible role of AhR in regulation of AKR1C9 expression. Taken together, both CYP1 and AKR1C9 appear to be AhR-regulated metabolic pathways, which may contribute to formation of pro-carcinogenic PAH metabolites in liver progenitor cells.
- MeSH
- benzopyren toxicita MeSH
- buněčné linie MeSH
- dimethylsulfoxid toxicita MeSH
- játra cytologie enzymologie MeSH
- kmenové buňky účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- peroxid vodíku toxicita MeSH
- polychlorované dibenzodioxiny analogy a deriváty toxicita MeSH
- polycyklické aromatické uhlovodíky metabolismus MeSH
- reaktivní formy kyslíku MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- regulace genové exprese enzymů účinky léků MeSH
- umlčování genů MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
