RESUMO
Amifostine is the most effective radioprotector known and the only one accepted for clinical use in cancer radiotherapy. In this work, the antigenotoxic effect of amifostine against gamma-rays was studied in Escherichia coli cells deficient in DNA damage repair activities. Assays of irradiated cells treated with amifostine showed that the drug reduced the genotoxicity induced by radiation in E. coli wild-type genotypes and in uvr, recF, recB, recB-recC-recF mutant strains, but not in recN defective cells. Thus, the mechanism of DNA protection by amifostine against gamma-radiation-induced genotoxicity appears to involve participation of the RecN protein that facilitates repair of DNA double-strand breaks. The results are discussed in relation to amifostine's chemopreventive potential.
Assuntos
Amifostina/farmacologia , Dano ao DNA/efeitos dos fármacos , Proteínas de Escherichia coli/metabolismo , Escherichia coli/efeitos dos fármacos , Raios gama , Protetores contra Radiação/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/efeitos da radiação , Enzimas de Restrição do DNA/genética , Enzimas de Restrição do DNA/metabolismo , Escherichia coli/genética , Escherichia coli/efeitos da radiação , Proteínas de Escherichia coli/genéticaRESUMO
Betaine-homocysteine S-methyltransferase (BHMT) is an enzyme that converts homocysteine (Hcy) to methionine using betaine as a methyl donor. Betaine also acts as osmolyte in kidney medulla, protecting cells from high extracellular osmolarity. Hepatic BHMT expression is regulated by salt intake. Hormones, particularly corticosteroids, also regulate BHMT expression in rat liver. We investigated to know whether the corticoadrenal activity plays a role in kidney BHMT expression. BHMT activity in rat kidneys is several orders of magnitude lower than in rat livers and only restricted to the renal cortex. This study confirms that corticosteroids stimulate BHMT activity in the liver and, for the first time in an animal model, also up-regulate the BHMT gene expression. Besides, unlike the liver, corticosteroids in rat kidney down-regulate BHMT expression and activity. Given that the classical effect of adrenocortical activity on the kidney is associated with sodium and water re-absorption by the distal tubule leading to volume expansion, by promoting lesser use of betaine as a methyl donor, corticosteroids would preserve betaine for its other role as osmoprotectant against changes in the extracellular osmotic conditions. We conclude that corticosteroids are, at least in part, responsible for the inhibition of BHMT expression and activity in rat kidneys.
Assuntos
Corticosteroides/metabolismo , Betaína-Homocisteína S-Metiltransferase/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Rim/metabolismo , Fígado/metabolismo , Adrenalectomia , Análise de Variância , Animais , Western Blotting , Primers do DNA/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Metilprednisolona/farmacologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Se presenta el caso de una paciente que muestra algunas de las alteraciones fenotipicas principales de la monosomia 1q4 (epicanto, micrognatia, microcefalia) y en la cual el estudio citogenético mediante la técnica de bandas G permitió datectar, en todas las metafases, una translocación 1:14, cuyo punto de ruptura en el cromosoma 1 coincide con los reportados para la delección que origina la monosomia