Aberrant DNA methylation is a common finding in AML and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced by low-level exposure to benzene, a widespread pollutant related to acute myeloid leukemia (AML) risk, in peripheral blood DNA of 78 gasoline station attendants (median personal airborne benzene, MPAB=61 µg/m3; range 11-478 µg/m3), 77 traffic police officers (MPAB=22 µg/m3; range 9-316 µg/m3), and 58 referents (MPAB=6 µg/m3; range <6-115 µg/m3). METHODS: Bisulfite-PCR Pyrosequencing was used to quantitate global, genome-wide DNA methylation in LINE-1 and Alu repetitive elements, and to examine gene-specific methylation of MAGE-1 and p15. In addition, we used allele-specific Pyrosequencing of the H19 gene to detect Loss of Imprinting (LOI). RESULTS: DNA methylation patterns differed across the three exposure groups, particularly for global methylation in LINE-1 (p=0.003) and methylation of p15 (p<0.001). Airborne benzene was associated with a significant reduction in global methylation in LINE-1 (-2.33%, p=0.009) and Alu (-1.00%, p=0.027), estimated for a 10-fold increase in benzene levels. Airborne benzene was also associated with hypermethylation in p15 (+0.35%; p=0.018) and hypomethylation in MAGE-1 (-0.49%; p=0.049). LOI, performed on subjects heterozygous for the G/A SNP located within the H19 imprinting center, was found only in exposed subjects (4/73, 5.5%), and no referents (0/23, 0.0%). However, LOI was not significantly associated with airborne benzene (p>0.20). CONCLUSIONS: Low-dose exposure to benzene, and possibly other AML carcinogens, may induce DNA methylation changes in healthy subjects that reproduce the altered epigenetic patterns found in malignant cells.
|Titolo:||Changes in methylation pattern among workers exposed to low doses of benzene|
|Relatore:||BERTAZZI, PIETRO ALBERTO|
|Data di pubblicazione:||22-gen-2008|
|Parole Chiave:||Methylation ; benzene|
|Settore Scientifico Disciplinare:||Settore MED/44 - Medicina del Lavoro|
|Citazione:||Changes in methylation pattern among workers exposed to low doses of benzene ; P.A. Bertazzi. - Milano : Università degli studi di Milano. DIPARTIMENTO DI MEDICINA DEL LAVORO - "CLINICA DEL LAVORO L.DEVOTO", 2008 Jan 22. ((20. ciclo, Anno Accademico 2006/2007.|
|Appare nelle tipologie:||13 - Tesi di dottorato discussa entro ottobre 2010|