Oxidative Stress and the Inorganic Carcinogens

Abstract

The metallic elements and their compounds include some very notable human carcinogens. The various inorganics that are considered clearly carcinogenic in humans include arsenic, beryllium, cadmium, and nickel, and their related compounds, as well as chromium(VI) compounds. For various other metals and metals compounds, there is clear evidence in rodents of carcinogenic potential but only limited or inadequate evidence of carcinogenesis in humans. These categories would include various compounds of lead, indium, cobalt, vanadium and iron. Most metallic elements that are associated with a carcinogenic response have a capacity to induce oxidative stress at levels relevant to carcinogenic mechanisms. The induction of oxidative stress by carcinogenic metals can be direct (e.g. Fenton-like chemistry) or indirect (e.g. glutathione consumption, inhibition of oxidative stress response enzymes). Oxidative stress may be a primary or secondary mechanism of carcinogenesis for an individual metal and could lead to direct DNA damage, or damage to DNA repair systems as a basis of genotoxicity. However, every metal shows distinct biological behaviors and requires investigation on a metal-by-metal basis. Metal-induced oxidative stress can also be associated with a variety of other disease states.