Figure 6.

Summary of the potential cellular processes modulating As^III toxicity in K562 cells revealed by CRISPR-based loss-of-function screening. As^III enters the cell through Aquaporin 3 (AQP3). As^III or its metabolites can have multiple cellular effects. As^III-induced oxidative stress could result from mitochondrial damage and/or from a direct effect on thioredoxin reductase (TrxR) and generation of SecTRAPs. As^III can have anti-proliferative effects by driving cell differentiation that is mediated by multiple cellular regulatory processes. Nrf2-based antioxidant response, intracellular selenium, intracellular zinc and export through ABCC1 can protect against As^III cytotoxicity.