Figure 1.

Complexity of signal initiation event(s) in NF-κB signaling induced by gentoxic agents. The ligand-receptor interaction represents the signal initiation event for NF-κB activation induced by a traditional canonical NF-κB inducer, such as TNFα (left). Genotoxic agents, such as IR (ionizing radiation), may induce different types of nuclear DNA damage and stress conditions, as well as induce other cellular stress conditions (right). Different DNA and cell stress conditions listed as examples are not meant to be comprehensive. The fundamental knowledge of the necessary and sufficient events that initiate NF-κB signaling pathways induced by genotoxic agents is currently incomplete. Because of the presence of concurrent molecular events induced by different genotoxic agents, more than one mechanism may be induced to control NF-κB activation with varying dominance and different kinetics.