Effect of cadmium and mercury on the nuclear retinoic acid receptors

The actions of retinoic acids (RA) are mediated by their cognate nuclear receptors--ligand inducible transcription factors (retinoic acid receptors (RAR)). Possible interactions of toxic heavy metals on the RAR system are of interest due to involvement of the RAR system in multiple systemic processes. We assayed cadmium chloride and mercury chloride for their influence on the RAR system in rat and in cell culture. Mercury chloride was observed to decrease the maximal binding capacity in vitro of RARs for all-trans RA in liver nuclear fraction containing sets of nuclear receptors by seventy percent at a concentration of 0.1 mmol/l, though not cadmium chloride. Neither mercury chloride nor cadmium chloride induced any changes with respect to mRNA levels of RAR and binding properties of nuclear receptor fraction for RA or retinoic acid responsive elements (RARE) in male Wistar rats receiving tap water with cadmium chloride (9.7 mg/l) or mercury chloride (11.5 mg/l) for six weeks. In rat pituitary GH4C1 cells, neither mRNA levels nor binding properties for RARE in cell culture were affected by non-toxic concentrations of these heavy metals. From the data obtained it is suggested that, in vivo, cadmium or mercury have no significant impact on RA nuclear receptor system.