Figure 1.

Asbestos induces genomic/epigenomic alterations driving malignant mesothelioma. Asbestos exposure induces ROS formation directly via the iron-induced Fenton reaction or indirectly by chronic inflammation (mesothelial cells and macrophages inflammatory cells). ROS exposure induces methylation of the gene promoter via a specific recognition site to which DNMT1 and PARP1 are recruited, linking DNA damage and DNA methylation. Alternatively, prolonged ROS exposure induces demethylation by oxidizing the 5-methycytosine to produce 5-hydroxymethylcytosine, which is catalyzed by ten-eleven translocation methylcytosine dioxygenase (TET) family of enzymes. Hypomethylation of genomic DNA is associated with genomic instability, which in combination with genetic alterations (chromosome deletion), both contribute to malignant transformation.