The reason for this is two-fold: 1) previous studies have indicated that while NOX4 generates significant levels of hydrogen peroxide, associated increases in superoxide radical generation are difficult to detect; and 2) CIS involves processes in various cellular compartments in addition to the mitochondria, including the DDR and gene expression changes in the nucleus, and H2O2 is a more stable molecule that is able to diffuse freely throughout the cell [58, 59]. This evidence concerns the gene NOX4 and in situ carcinoma.