Occupational
factors contribute significantly to global burden of chronic diseases like
cancer and neurobehavioural disorders. A clear understanding of underlying
mechanisms is crucial for prevention. Epigenetics is currently of major
interest, as it provides insight in how cells respond to environmental stimuli.
In order to
investigate whether occupational exposure induces epigenetic alterations
similar as observed in chronic diseases, we carried out several translation
studies in workers exposed to solvents and carbon nanotubes to validate DNA
methylation alterations observed in in
vitro and animal studies.
Global DNA
methylation and demethylation patterns were studied using LC-MS/MS. Genome-wide
assessment of DNA methylation was performed with Infinium HumanMethylation450
BeadChip Array. Levels of methylation of specific genes were measured by
pyrosequencing.
We observed in
lab settings, global DNA hypomethylation in TK6 cells after exposure to several
solvents. DNA hypermethylation was observed in blood DNA of individuals working
with solvents. Carbon nanotubes altered in vitro methylation and gene
expression levels of 17 genes involved in the regulation of transcription, cell
development and other cellular processes.
In mice, nanoparticles affected methylation of ATM gene but not the global
DNA methylation and hydroxymethylation levels. In exposed workers a significant
hypermethylation was observed for DNMT1 in bloodcells.
Occupationl
exposure to solvents and particles induce global and gene specific DNA
methylation alterations. It remains to be investigated which epigenetic
response to occupational stressors leads to pathological signalling events
initiating the disease process.
Journal Section | Articles |
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Authors | |
Publication Date | February 16, 2017 |
Published in Issue | Year 2017 Volume: Volume 2 Issue: İssue 1 (1) - 2.İnternational Congress Of Forensic Toxicology |