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Analysis of the Effects of Cr(VI) Exposure on mRNA Modifications.
Chem Res Toxicol ; 32(10): 2078-2085, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433169
ABSTRACT
Hexavalent chromium [Cr(VI)] compounds that are generated during industrial processes are widely recognized as highly toxic and carcinogenic. It has been reported that exposure to Cr(VI) can produce some chromium intermediates and reactive oxygen species (ROS), which causes DNA damages, genetic instability, and eventually leads to the elevated risk of various diseases including cancers. In recent years, it has been proposed that epigenetic-based mechanisms may involve in the toxic heavy metals-induced cytotoxicity and mutagenicity besides the genetic-based mechanisms. However, whether Cr(VI) could impose its cytotoxic effect through dysregulating the RNA epigenetic modifications remains poorly defined. We systematically investigated the effects of Cr(VI) exposure on 14 kinds of modifications in mRNA of HEK293T cells. We found that Cr(VI) exposure can induce an obvious decrease of inosine in mRNA. In addition, we observed that the expression level of the adenosine deaminase acting on RNA (ADAR1) was significantly decreased upon Cr(VI) exposure, which could be responsible for the induced decrease of inosine in mRNA by Cr(VI) exposure. Together, we demonstrated that Cr(VI) could interrupt A-to-I RNA editing in mRNA, which may eventually lead to the cytotoxicity and mutagenicity.

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Aspecto clínico: Etiologia Idioma: Inglês Revista: Chem Res Toxicol Assunto da revista: Toxicologia Ano de publicação: 2019 Tipo de documento: Artigo