Toxicité de la dioxine : rôle des protéines PAS

Abstract

La dioxine occasionne des risques averes qui concernent la securite sanitaire des aliments et la sante publique. Un traitement mediatique considerable, souvent sans nuance, fait de ce contaminant un " ennemi public numerol 1 ". Certes, sa grande toxicite chez l' animal de laboratoire est etablie; cependant, les connaissances scientifiques actuelles n' autorisent pas l' extrapolation ex abrupto de cette toxicite a l' homme. Des donnees epidemiologiques et experimentales suggerent une moindre susceptibilite, a la dioxine, de l' homme compare a la souris. Mais en l' absence de donnees incontestables relatives a l' homme, le debat et la polemique perdurent entre specialistes. Dans ce contexte, il est delicat pour l' autorite administrative de definir les normes relatives a la presence de dioxine dans l' environnement ou les aliments, garantissant l' innocuite pour la population. Une meilleure comprehension du mode d' action toxique de la dioxine et de la specificite de la sensibilite humaine permettraient de preciser et d' harmoniser les politiques publiques concernant ce contaminant. Dans cette attente, un legitime principe de precaution impose une tolerance minimale.

Dioxin derivatives cause a major and diverse toxicity in rodents while their effects on humans remain controversial. Some recent events show that a risk for human exposure is obvious. A better understanding of the consequences of these chemicals on human biology is needed. Until then, safety procedures have to limit human exposure to a minimum. This document offers a presentation of this family of xenobiotics, their origins and their toxic effects on animal and cellular models compared to their consequences in some cases of human exposure ('Seveso'). A molecular signaling pathway for most of the biological effects of dioxin is described. It includes a pair of 'PAS'-domain proteins: a dioxin-attivated receptor (AHR) and its heterodimeric partner (Arnt). The resulting complex activates a battery of target genes whose nature do not authorizes yet the full understanding of the toxicity of dioxins. Null animal models were helpful in identifying some developmental and physiological implications of the dioxin-activated pathway. [References: 48]