Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review).
Cadmium is an important toxic environmental heavy metal. Occupational and environmental pollution with cadmium results mainly from mining, metallurgy industry and manufactures of nickel-cadmium batteries, pigments and plastic stabilizers. Important sources of human intoxication are cigarette smoke as well as food, water and air contaminations. In humans, cadmium exposures have been associated with cancers of the prostate, lungs and testes. Acute exposures are responsible for damage to these organs. Chronic intoxication is associated with obstructive airway disease, emphysema, irreversible renal failure, bone disorders and immuno-suppression. At the cellular level, cadmium affects proliferation, differentiation and causes apoptosis. It has been classified as a carcinogen by the International Agency for Research on Cancer (IARC). However, it is weakly genotoxic. Indirect effects of cadmium provoke generation of reactive oxygen species (ROS) and DNA damage. Cadmium modulates also gene expression and signal transduction, reduces activities of proteins involved in antioxidant defenses. Several studies have shown that it interferes with DNA repair. The present review focuses on the effects of cadmium in mammalian cells with special emphasis on the induction of damage to DNA, membranes and proteins, the inhibition of different types of DNA repair and the induction of apoptosis. Current data and hypotheses on the mechanisms involved in cadmium genotoxicity and carcinogenesis are outlined.
Bertin
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Institut Curie-UMR 2027 CNRS Génotoxicologie et cycle cellulaire, LCR V28 du CEA, centre universitaire, 91405 Orsay cedex, France.
Averbeck
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D
D002104:Cadmium / Q000494:pharmacology* / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects
D009153:Mutagens; D002104:Cadmium