Induction of Human Squamous Cell-Type Carcinomas by Arsenic

Figure 1

Carcinogenic mechanisms of arsenic transformation. Ingested arsenic undergoes a biotransformation process. (1) Biotransformation could lead to arsenic excretion, when conjugated with glutathione. (2) Biotransformation generates reactive oxygen species (ROS), namely, superoxide anions (O₂⁻), hydrogen peroxide (H₂O₂), hydroxyl radicals (OH), that induce single-strand (ssDNA) and double-strand (dsDNA) breaks by inducing oxidative damage. The process can also inhibit DNA break repair mechanisms for ssDNA breaks (base excision repair (BER)) and for dsDNA breaks (homologous recombination (HR) and/or nonhomologous end joining (NHEJ)). Additionally, ROS derived from arsenic biotransformation can act as cocarcinogens, for example, increasing damage potential of ultraviolet (UV) light. Furthermore, the requirement of S-adenosyl methionine (SAM) for arsenic biotransformation can lead to depletion of SAM, which is the substrate for DNA methylation.