Figure 9. Model for the potentiation of sequence rearrangements induced by endogenous and exogenous DNA damage by inflammation-associated cell proliferation.

Cell proliferation associated with inflammation may be induced by RONS released from inflammatory cells. Regeneration after inflammation also involves cell proliferation to replenish cells lost to inflammation-induced tissue damage. DNA replication is increased in proliferation, and DNA damage during replication can lead to fork breakdown and the formation of DSBs. These DSBs are repaired by HR, but HR can result in LOH, sequence rearrangements, and point mutations. Thus, cell proliferation potentiates the deleterious effect of both endogenous (RONS-induced) and exogenous (exposure-induced) DNA damage, potentially contributing to cancer initiation and recurrence. See text for details.