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Int. J. Mol. Sci. 2011, 12(12), 9576-9595; doi:10.3390/ijms12129576

Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

1
Department of Life Science, Dongguk University, 30 Pildong-ro 1-gil (26 Pildong 3-ga), Jung-gu, Seoul 100-715, Korea
2
Institute of Environmental Medicine for Green Chemistry, Dongguk University, 30 Pildong-ro 1-gil (26 Pildong 3-ga), Jung-gu, Seoul 100-715, Korea
*
Author to whom correspondence should be addressed.
Received: 13 September 2011 / Revised: 28 October 2011 / Accepted: 12 December 2011 / Published: 20 December 2011
(This article belongs to the Special Issue Biomarkers 2011)
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Abstract

Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.
Keywords: carcinogenicity; DNA damage; DNA repair; genotoxicity; heavy metal; oxidative stress carcinogenicity; DNA damage; DNA repair; genotoxicity; heavy metal; oxidative stress
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Koedrith, P.; Seo, Y.R. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers. Int. J. Mol. Sci. 2011, 12, 9576-9595.

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