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.

Changes in methylation pattern among workers exposed to low doses of benzene / V. Bollati ; P.A. Bertazzi. DIPARTIMENTO DI MEDICINA DEL LAVORO - "CLINICA DEL LAVORO L.DEVOTO", 2008 Jan 22. 20. ciclo, Anno Accademico 2006/2007.

Changes in methylation pattern among workers exposed to low doses of benzene

V. Bollati
2008

Abstract

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.
22-gen-2008
Methylation ; benzene
Settore MED/44 - Medicina del Lavoro
BERTAZZI, PIETRO ALBERTO
Doctoral Thesis
Changes in methylation pattern among workers exposed to low doses of benzene / V. Bollati ; P.A. Bertazzi. DIPARTIMENTO DI MEDICINA DEL LAVORO - "CLINICA DEL LAVORO L.DEVOTO", 2008 Jan 22. 20. ciclo, Anno Accademico 2006/2007.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/60902
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