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.
Metodologie molecolari e genetiche nello studio degli effetti di agenti occupazionali ed ambientali : l'esempio del "Seveso molecular epidemiology project" / A. Baccarelli, A.C. Pesatori, D. Consonni, D. Patterson J. r., M. Bonzini, B. Marinelli, J.A. Grassman, P.A. Bertazzi, M.T. Landi. - In: GIORNALE ITALIANO DI MEDICINA DEL LAVORO ED ERGONOMIA. - ISSN 1592-7830. - 26:suppl al n. 4(2004), pp. 22-23. ((Intervento presentato al 67. convegno Congresso nazionale SIMLII : Monitoraggio biologico e ambienti confinati non industriali : aggiornamenti e prospettive tenutosi a Sorrento nel 2004.
Metodologie molecolari e genetiche nello studio degli effetti di agenti occupazionali ed ambientali : l'esempio del "Seveso molecular epidemiology project"
A. BaccarelliPrimo
;A.C. PesatoriSecondo
;M. Bonzini;B. Marinelli;P.A. BertazziPenultimo
;
2004
Abstract
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.Pubblicazioni consigliate
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