Roles of dioxins and heavy metals in cancer and neurological diseases using ROS-mediated mechanisms.
Oxidants have critical functions inside healthy and unhealthy cells. Deregulated cell cycle and apoptosis, both regulated by oxidative stress, have been described as hallmarks of mitotic (cancer) and postmitotic (neuronal) cells. This review provides an updated revision of the oxidant effects of some environmental contaminants such as dioxins and the heavy metals cadmium, cobalt, and copper. Dioxins exert their toxic actions by acting on phase I and phase II enzymes, such as cytochromes P450, superoxide dismutase, and glutathione peroxidase, promoting cell proliferation, growth arrest, and apoptosis, affecting cancer homeostasis and neuronal function. Heavy metals manifest cytotoxic effects in various cells and tissues, and tight regulation of metals is essential to the health of organisms. Cadmium modulates gene expression and signal transduction and reduces activities of proteins involved in antioxidant defense, interfering with DNA repair and modifying cancer development and brain function. Cobalt provokes generation of reactive oxygen species and DNA damage in cancer cells and brain tissues, altering proliferation and differentiation and causing apoptosis. Copper is a key metal in cell division processes in both normal and tumor cells. Copper also has been shown to have an important role in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis.
Matés
José M
JM
Departmento de Biología Molecular y Bioquímica, Facultad de Ciencias, Campus de Teatinos, Universidad de Málaga, 29071 Málaga, Spain. jmates@uma.es
Segura
Juan A
JA
Alonso
Francisco J
FJ
Márquez
Javier
J
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004147:Dioxins / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects*; D006801:Humans; D019216:Metals, Heavy / Q000009:adverse effects*; D009369:Neoplasms / Q000139:chemically induced* / Q000473:pathology; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D004147:Dioxins; D004785:Environmental Pollutants; D019216:Metals, Heavy; D017382:Reactive Oxygen Species