Mechanisms of cadmium carcinogenesis.
Cadmium (Cd), a heavy metal of considerable occupational and environmental concern, has been classified as a human carcinogen by the International Agency for Research on Cancer (IARC). The carcinogenic potential of Cd as well as the mechanisms underlying carcinogenesis following exposure to Cd has been studied using in vitro cell culture and in vivo animal models. Exposure of cells to Cd results in their transformation. Administration of Cd in animals results in tumors of multiple organs/tissues. Also, a causal relationship has been noticed between exposure to Cd and the incidence of lung cancer in human. It has been demonstrated that Cd induces cancer by multiple mechanisms and the most important among them are aberrant gene expression, inhibition of DNA damage repair, induction of oxidative stress, and inhibition of apoptosis. The available evidence indicates that, perhaps, oxidative stress plays a central role in Cd carcinogenesis because of its involvement in Cd-induced aberrant gene expression, inhibition of DNA damage repair, and apoptosis.
Molecular Carcinogenesis Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. pjoseph1@cdc.gov
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D018570:Risk Assessment
D002274:Carcinogens, Environmental; D002104:Cadmium