In 1997, IARC classified 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as carcinogenic to humans, based on sufficient evidence from animal data and limited evidence from human data. A key role in the IARC classification was played by the well-defined mechanism of TCDD action involving the activation of the Arylhydrocarbon Receptor (AhR). Experimental animal and in-vitro studies indicate that AhR levels decrease following TCDD binding. Nearly 20 years after the Seveso accident, we found a decrease in AhR mRNA levels in TCDD-exposed subjects. AhR transcript levels were correlated with plasma TCDD concentrations. Our results may reflect a down-regulation of AhR, similar to that observed in most receptorial systems. We demonstrated, for the first time in humans, that TCDD-related regulation of the AhR pathway, previously observed in experimental studies, may also occur in exposed subjects. Our data are important for extrapolating AhR-mediated effects from experimental models to humans.
|Translated title of the contribution||Molecular and genetic methods for studying the effects of occupational and environmental agents: The seveso molecular epidemiology project|
|Number of pages||2|
|Journal||Giornale Italiano di Medicina del Lavoro ed Ergonomia|
|Issue number||4 SUPPL.|
|State||Published - Nov 26 2004|
All Science Journal Classification (ASJC) codes
- Public Health, Environmental and Occupational Health