Approximately 20 years after the Seveso, Italy accident, we conducted a population-based study to evaluate the impact of 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) exposure upon immune and mechanistically based biomarkers of dioxin response in humans. TCDD toxic effects are known to be mediated by the aryl-hydrocarbon receptor (AhR). We randomly selected 62 study subjects from the highest exposed zones and 59 from the surrounding non-contaminated area. Current lipid-adjusted plasma TCDD concentrations in these subjects ranged from 3.5 to 90ng/kg (or ppt) and were negatively associated with plasma IgG concentrations (r=-0.35;P=0.0002). The expression of genes in the AhR-dependent pathway, including AhR, aryl-hydrocarbon receptor nuclear translocator (ARNT), CYP1A1, and CYP1B1 transcripts, and the CYP1A1-associated 7-ethoxyresorufin-O- deethylase (EROD) activity was measured in lymphocytes. AhR mRNA levels in uncultured lymphocytes were negatively associated with plasma TCDD (P=0.03). When mitogen-induced lymphocytes were cultured with 10nM TCDD, all AhR-dependent genes were induced 1.2- to 13-fold. In these cells, plasma TCDD was associated with decreased EROD activity. Markers within the AhR pathway were correlated with one another. Our findings suggest the presence of long-term effects in the subjects exposed to TCDD after the Seveso accident.
Aryl-hydrocarbon receptor-dependent pathway and toxic effects of TCDD in humans : a population-based study in Seveso, Italy / A. Baccarelli, A.C. Pesatori, S.A. Masten, D.G. Jr. Patterson, L.L. Needham, P. Mocarelli, N.E. Caporaso, D. Consonni, J.A. Grassman, P.A. Bertazzi, M.T. Landi. - In: TOXICOLOGY LETTERS. - ISSN 0378-4274. - 149:1-3(2004 Apr 01), pp. 287-293.
|Titolo:||Aryl-hydrocarbon receptor-dependent pathway and toxic effects of TCDD in humans : a population-based study in Seveso, Italy|
BACCARELLI, ANDREA (Primo)
PESATORI, ANGELA CECILIA (Secondo)
BERTAZZI, PIETRO ALBERTO (Penultimo)
|Parole Chiave:||Aryl-hydrocarbon receptor; Dioxin; Molecular epidemiology; Population-based study; TCDD|
|Settore Scientifico Disciplinare:||Settore MED/44 - Medicina del Lavoro|
|Data di pubblicazione:||1-apr-2004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.toxlet.2003.12.062|
|Appare nelle tipologie:||01 - Articolo su periodico|