[Mechanisms of action for metallic elements and their species classified carcinogen R 45 and R 49 by EU].
In this paper we will deal with mechanism of carcinogenic action of metallic elements and their species (arsenic, beryllium, cadmium, cobalt, chromium, nickel) identified by EU as carcinogen R 45 or R 49. The carcinogenic effect depended on the ability of to penetrate the cell and interacted with the target sites, therefore the state of oxidation, charging, the solubility, type of binding, stereochemistry and the ability to interact with other xenobiotics were crucial. The carcinogenic metallic elements classified R45 or R49 are essentially weak mutagen and do not form adducts with the DNA as initial step of their carcinogenicity In spite of the wide range of metallic elements physicochemical properties, some common general mechanisms of carcinogenesis emerge:from the induction of oxidative stress, to inhibition of DNA repair, from activation of mitogenic signalling, to epigenetic modification of gene expression. However, each species lead to specific molecular interactions and were subject to different bioavailability. It has been also strongly supported the hypothesis that the metallic elements may act as a co-carcinogen with other organic compounds, for example with PAH.
Apostoli
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Dipartimento di Medicina Sperimentale e Applicata, Sezione di Medicina del Lavoro e Igiene Industriale, Università degli Studi di Brescia, Italy. apostoli@med.unibs.it
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