Disruption of retinoid signalling by 2,3,7,8-TCDD and phthalates on P19/A15 cell line
| Authors | |
|---|---|
| Year of publication | 2005 |
| Type | Article in Proceedings |
| Conference | Joint Conference of Scandinavian Society of Cell Toxicology and Estonian Society of Toxicology |
| MU Faculty or unit | |
| Citation | |
| Field | Environment influence on health |
| Keywords | retinoid; dioxin; phtalates; disruption |
| Description | Natural retinoids - vitamin A and its metabolites - are very important signalling molecules in eukaryotic organisms. They are necessary for vision, play an important role in cell growth, differenciation and apoptosis, influence embryonic development and function of nervous and immunity system, etc. In our study, we used an embryonic cell line P19/A15 stably transfected with luciferase gene under control of retinoic acid receptor (RAR) for investigation of effects of eight different phtalates and 2,3,7,8 tetrachlorodibenzodioxin (TCDD) on retinoid signalling. Disruption of retinoid homeostasis as a result of exposure to dioxin-like substances has been described elsewhere. Furthermore, some studies suggested also direct downregulation of retinoid-dependent effects by TCDD. Phthalates widespread polutants released particularly from chemical industry have a similar structure to retinoids and for that reason we decided to investigate their possible interaction with retinoid pathway. P19/A15 cell line is a pluripotent embryonic line that is able to differentiate into cells of a variety of tissues. In this study, we compared retinoid disruptive effects caused by studied substances in original embryonic cells and in those differentiated into cells of primitive ectoderm. Suppression of retinoid-dependent luciferase activity by nanomolar concentrations of TCDD was observed in differentiated cells while no or only weak effect was detected in pluripotent cells. This may be caused by increase in number of nuclear receptors in cells during differentiation. Some phthalates were also shown to suppress retinoid-like signaling. |
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