Interference of some environmental contaminants with retinoid signaling in vitro

Abstract

Retinoids are dietary hormones important during proliferation, differentiation and apoptosis.They act mainly through nuclear receptors for retinoic acid, RARs and RXRs. Disruption of these signaling pathways can lead to several adverse effects especially during embryonic development. Using pluripotent P19/A15 cell we tested whether some polycyclic aromatic hydrocarbons (PAHs), their N-heterocyclic analogs and some personal care products(UV filters, parabens) can interfere with retinoid signaling. Studied compounds were tested for direct activation of RAR/RXR signaling pathway, but also modulation of the response of natural ligand all-trans retinoic acid (ATRA) by studied compounds was tested. No direct activation was found for studied PAHs and N-PAHs, however, some of these compounds modulated the response of ATRA. Downregulation of the response was observed mostly for 2 and 3-ring N-PAHs, while 4 and 5-ring PAHs and N-PAHs mostly up-regulated the response of ATRA. Interference of personal care products with retinoid signaling in P19/A15 assay is further discussed in the second part of this study.