Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms
Figure 1
Arsenic-induced DNA strand breaks. After ingestion, iAs biotransformation process could lead to iAs excretion, mainly conjugated with Glutathione (GSH). On the other hand, biotransformation process may generate reactive oxygen species (ROS), probably in a specific sequence: superoxide anions (), hydrogen peroxide (H2O2), and hydroxyl radicals (·OH). These species can induce both single-strand (ssDNA) and double-strand (dsDNA) breaks by inducing oxidative damage. In parallel, they can inhibit DNA break repair mechanisms both for ssDNA breaks (mainly base excision repair [BER]) and for dsDNA breaks (homologous recombination [HR] and/or nonhomologous end joining [NHEJ]). Additionally, ROS derived from iAs biotransformation can act as cocarcinogens, for example, increasing damage potential of ultraviolet (UV) light. All these events could be associated, in part, to iAs-related carcinogenic mechanism.
