Schematic presentation of the proposed mechanism by which cytokines may promote genomic instability in chronic inflammatory conditions. Cytokines with growth factor activity may promote replication stress favouring the formation of DSBs. In addition, several cytokines induce the formation of RONS which in turn may cause DNA damage, including DNA cross-links, single- or double-strand breaks, and oxidative DNA damage with formation of 8-hydroxydeoxyguanosine (8-OHdG). Both mechanisms may provide a mechanism linking cytokine expression with genomic instability. MAPK: mitogen-activated protein kinase; JAK-STAT3: Janus kinase - Signal Transducer and Activator of Transcription 3; NF-κB: Nuclear Factor-κB; AP-1: Activator Protein 1; OPN: Osteopontin; R: Receptor; RONS: Reactive Oxygen/Nitrogen Species; NAD(P)H oxidase: Nicotinamide Adenine Dinucleotide Phosphate-oxidase; iNOS: inducible Nitric Oxide Synthase.
