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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The effects of dietary supplementation of methionine on genomic stability and p53 gene promoter methylation in rats

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Author(s):
Do Amaral, Cada Lira [1] ; Bueno, Rafaela de Barros e Lima [1] ; Burim, Regislaine Valeria [1] ; Costa Queiroz, Regina Helena [1] ; Pires Bianchi, Maria de Lourdes [1] ; Greggi Antunes, Lusania Maria [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS; v. 722, n. 1, p. 78-83, MAY 18 2011.
Web of Science Citations: 12
Abstract

Methionine is a component of one-carbon metabolism and a precursor of S-adenosylmethionine (SAM), the methyl donor for DNA methylation. When methionine intake is high, an increase of S-adenosylmethionine (SAM) is expected. DNA methyltransferases convert SAM to S-adenosylhomocysteine (SAH). A high intracellular SAH concentration could inhibit the activity of DNA methyltransferases. Therefore, high methionine ingestion could induce DNA damage and change the methylation pattern of tumor suppressor genes. This study investigated the genotoxicity of a methionine-supplemented diet. It also investigated the diet's effects on glutathione levels, SAM and SAH concentrations and the gene methylation pattern of p53. Wistar rats received either a methionine-supplemented diet (2% methionine) or a control diet (0.3% methionine) for six weeks. The methionine-supplemented diet was neither genotoxic nor antigenotoxic to kidney cells, as assessed by the comet assay. However, the methionine-supplemented diet restored the renal glutathione depletion induced by doxorubicin. This fact may be explained by the transsulfuration pathway, which converts methionine to glutathione in the kidney. Methionine supplementation increased the renal concentration of SAH without changing the SAM/SAH ratio. This unchanged profile was also observed for DNA methylation at the promoter region of the p53 gene. Further studies are necessary to elucidate this diet's effects on genomic stability and DNA methylation. (C) 2011 Elsevier ay. All rights reserved. (AU)