Figure 4.

Cooperative cytotoxic mechanism between DNMT inhibitors and radiation. Ionizing radiation induces DNA base damage, single-strand breaks, and double-strand breaks (DSBs). All of these errors can be rapidly repaired except for DSBs, which if not repaired are considered lethal. The cytotoxic effect of DNMT inhibitors in close proximity to a radiation-induced single-strand break can act synergistically to make the defect significantly more difficult to repair, consequently resulting in the induction of cellular death.