A possible novel toxic index for dioxins/PCBs -Is dioxin more toxic than OH-PCB?

Abstract

Polychrolinated biphenyls (PCBs) and dioxins (PCDD, PCDF, coplaner-PCB) are the environmental chemicals that may affect the growth and homeostasis of many organs. WHO determined toxic index of dioxins as toxicity equivalent factor (TEF). However, we reported previously that the most toxic dioxin (TCDD) did not affect on thyroid hormone (TH) receptor (TR)-mediated transcription. On the other hand, a hydroxylated-PCB5005 whose TEF was almost negligible, strongly suppressed the transcription. In this study, we performed a reporter gene assay with several PCBs and dioxins, and observed opposite tendency from TEF: many PCBs with little TEF showed a greater effect than dioxins. Furthermore the magnitude of suppression by PCBs and PCDF in neuroblastoma derived cell line was greater than that in fibroblast derived cell line. To analyze further the effect of these chemicals in TR-TH response element (TRE) binding, electrophoretic mobility shift assay (EMSA) was performed. PCB congeners that suppressed TR-mediated transcription dissociated TR from TRE, indicating that PCB action is exerted through this mechanism.These results suggest that TEF of dioxins and PCBs do not always correctly indicate their toxicity. The suppression of TR-mediated transcription by PCBs and dioxins should be incorporated to construct a novel index of those chemicals. [J Physiol Sci. 2006;56 Suppl:S99]