Interference of contaminated sediment extracts and environmental pollutants with retinoid signaling.
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.
Novák
Jirí
J
Research Centre for Environmental Chemistry and Ecotoxicology, Masaryk University, Kamenice 3, 625 00 Brno, Czech Republic.
Benísek
Martin
M
Pacherník
Jirí
J
Janosek
Jaroslav
J
Sídlová
Tereza
T
Kiviranta
Hannu
H
Verta
Matti
M
Giesy
John P
JP
Bláha
Ludek
L
Hilscherová
Klara
K
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D018236:Carcinoma, Embryonal / Q000473:pathology; D045744:Cell Line, Tumor; D004147:Dioxins / Q000032:analysis / Q000633:toxicity; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005387:Finland; D005663:Furans / Q000032:analysis / Q000633:toxicity; D017930:Genes, Reporter; D019015:Geologic Sediments / Q000737:chemistry*; D049409:Luciferases, Firefly / Q000235:genetics; D010795:Phthalic Acids / Q000032:analysis / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity; D012176:Retinoids / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D015398:Signal Transduction; D014212:Tretinoin / Q000032:analysis / Q000633:toxicity
D004147:Dioxins; D004785:Environmental Pollutants; D005663:Furans; D010795:Phthalic Acids; D011084:Polycyclic Aromatic Hydrocarbons; D012176:Retinoids; D014212:Tretinoin; D049409:Luciferases, Firefly