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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Oxidative stress modulates DNA methylation during melanocyte anchorage blockade associated with malignant transformation

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Autor(es):
Campos, Ana C. E. ; Molognoni, Fernanda ; Melo, Fabiana H. M. ; Galdieri, Luciano C. ; Carneiro, Célia R. W. ; D'Almeida, Vânia ; Correa, Mariangela ; Jasiulionis, Miriam G.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: Neoplasia; v. 9, n. 12, p. 1111-1121, Dec. 2007.
Área do conhecimento: Ciências Biológicas - Microbiologia
Assunto(s):Morte celular   Anoikis   Carcinógenos   Metilação de DNA   Estresse oxidativo
Resumo

Both oxidative/nitrosative stress and alterations in DNA methylation are observed during carcinogenesis of different tumor types, but no clear correlation between these events has been demonstrated until now. Melanoma cell lines were previously established after submitting the nontumorigenic melanocyte lineage, melan-a, to cycles of anchorage blockade. In this work, increased intracellular oxidative species and nitric oxide levels, as well as alterations in the DNA methylation, were observed after melan-a detachment, which were also associated with a decrease in intracellular homocysteine (Hcy), an element in the methionine (universal methyl donor) cycle. This alteration was accompanied by increase in glutathione (GSH) levels and methylated DNA content. Furthermore, a significant increase in dnmt1 and 3b expression was identified along melan-a anchorage blockade. lG-Nitro-l-arginine methyl esther (l-NAME), known as a nitric oxide synthase (NOS) inhibitor, and N-acetyl-l-cysteine (NAC) prevented the increase in global DNA methylation, as well as the increase in dnmt1 and 3b expression, observed during melan-a detachment. Interestingly, both l-NAME and NAC did not inhibit nitric oxide (NO) production in these cells, but abrogated superoxide anion production during anchorage blockade. In conclusion, oxidative stress observed during melanocyte anchorage blockade seems to modulate DNA methylation levels and may directly contribute to the acquisition of an anoikis-resistant phenotype through an epigenetic mechanism. (AU)

Processo FAPESP: 06/61293-1 - Contribuição da metilação de DNA na carcinogênese
Beneficiário:Miriam Galvonas Jasiulionis
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 02/06935-7 - Controle epigenético da progressão tumoral de melanócitos
Beneficiário:Joel Machado Junior
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores