The search for new targets for mitigation of metal toxicity based on molecular pathways of action: A case study using cadmium and iron

Abstract Cadmium is a nonessential heavy metal, ubiquitous in nature with a long half-life in human beings. It is widely used in various industrial applications such as toy and jewelry making and is one of the key constituents of tobacco and cigarette smoke. Cadmium, both at occupational and environmental levels, has been implicated in the causation of cancerous and noncancerous health outcomes. In comparison, iron is an essential metal and is a constituent of hemoglobin and many vital enzymes and proteins and plays a pivotal role in human health. However, increased consumption of iron from fortified diets and iron supplements presents opportunities for exposure to supraphysiologic iron concentrations and toxicity. Additionally, hereditary iron disorders (thalassemia, hereditary hemochromatosis), other disease conditions such as cancer and kidney diseases, and certain environmental exposures (e.g., steel-welding fumes, asbestos, and air pollution) could also lead to iron toxicity with disturbed homeostasis mechanisms affecting intracellular and systemic regulation of iron. Chelation therapy has traditionally been used to mitigate the toxicity of metals. This talk will present the results of systematic reviews and analyses for both cadmium and iron toxicity and highlight the diverse molecular pathways by which these metals can elicit toxic effects. Using the examples of cadmium and iron, I will discuss some recent advances in our understanding of the molecular mechanisms of metal toxicity and how this information can be used to identify novel targets for toxicity mitigation. (The views expressed in this abstract are those of the author and do not necessarily reflect the views or policies of EPA.) Citation Format: Anuradha Mudipalli. The search for new targets for mitigation of metal toxicity based on molecular pathways of action: A case study using cadmium and iron [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A42.