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Interference of contaminated sediment extracts and environmental pollutants with retinoid signaling
J Novak, M Benisek, J Pachernik, J Janosek, T Sidlova, H Kiviranta, M Verta, JP Giesy, L Blaha, K Hilscherova
Language English Country United States
Document type Financing, Organized
NLK
ProQuest Central
from 2005-01-01 to 2009-12-31
Health & Medicine (ProQuest)
from 2005-01-01 to 2009-12-31
Public Health Database (ProQuest)
from 2005-01-01 to 2009-12-31
- MeSH
- Biological Assay methods MeSH
- Dioxins analysis toxicity MeSH
- Carcinoma, Embryonal pathology MeSH
- Financing, Organized MeSH
- Furans analysis toxicity MeSH
- Geologic Sediments chemistry MeSH
- Risk Assessment MeSH
- Phthalic Acids analysis toxicity MeSH
- Environmental Pollutants analysis toxicity MeSH
- Luciferases, Firefly genetics MeSH
- Cell Line, Tumor MeSH
- Polycyclic Aromatic Hydrocarbons analysis toxicity MeSH
- Genes, Reporter MeSH
- Retinoids genetics metabolism MeSH
- Signal Transduction MeSH
- Tretinoin analysis toxicity MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Geographicals
- Finland MeSH
Retinoids are known to regulate important processes such as differentiation, development, and embryogenesis. Some effects, such as malformations in frogs or changes in metabolism of birds, could be related to disruption of the retinoid signaling pathway by exposure to organic contaminants. A new reporter gene assay has been established for evaluation of the modulation of retinoid signaling by individual chemicals or environmental samples. The bioassay is based on the pluripotent embryonic carcinoma cell line P19 stably transfected with the firefly luciferase gene under the control of a retinoic acid-responsive element (clone P19/ A15). The cell line was used to characterize the effects of individual chemicals and sediments extracts on retinoid signaling pathways. The extracts of sediments from the River Kymi, Finland, which contained polychlorinated dioxins and furans and polycyclic aromatic hydrocarbons (PAHs), significantly increased the potency of all-trans retinoic acid (ATRA), while no effect was observed with the extract of the sediment from reference locality. Considerable part of the effect was caused by the labile fraction of the sediment extracts. Also, several individual PAHs potentiated the effect of ATRA; on the other hand, 2,3,7,8-tetrachlorodibenzo-p-dioxin and several phthalates showed slightly inhibiting effect. These results suggest that PAHs could be able to modulate the retinoid signaling pathway and that they could be responsible for a part of the proretinoid activity observed in the sediment extracts. However, the effects of PAHs on the retinoic acid signaling pathways do not seem to be mediated directly by crosstalk with aryl hydrocarbon receptor.
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- $a Retinoids are known to regulate important processes such as differentiation, development, and embryogenesis. Some effects, such as malformations in frogs or changes in metabolism of birds, could be related to disruption of the retinoid signaling pathway by exposure to organic contaminants. A new reporter gene assay has been established for evaluation of the modulation of retinoid signaling by individual chemicals or environmental samples. The bioassay is based on the pluripotent embryonic carcinoma cell line P19 stably transfected with the firefly luciferase gene under the control of a retinoic acid-responsive element (clone P19/ A15). The cell line was used to characterize the effects of individual chemicals and sediments extracts on retinoid signaling pathways. The extracts of sediments from the River Kymi, Finland, which contained polychlorinated dioxins and furans and polycyclic aromatic hydrocarbons (PAHs), significantly increased the potency of all-trans retinoic acid (ATRA), while no effect was observed with the extract of the sediment from reference locality. Considerable part of the effect was caused by the labile fraction of the sediment extracts. Also, several individual PAHs potentiated the effect of ATRA; on the other hand, 2,3,7,8-tetrachlorodibenzo-p-dioxin and several phthalates showed slightly inhibiting effect. These results suggest that PAHs could be able to modulate the retinoid signaling pathway and that they could be responsible for a part of the proretinoid activity observed in the sediment extracts. However, the effects of PAHs on the retinoic acid signaling pathways do not seem to be mediated directly by crosstalk with aryl hydrocarbon receptor.
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