title: The effects of dietary supplementation of methionine on genomic stability and p53 gene promoter methylation in rats.
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.
authors: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil. amaral.catia@yahoo.com.br
authors: Cátia Lira Do
authors: CL
authors: Amaral
authors: Rafaela de Barros E Lima
authors: Rde B
authors: Bueno
authors: Regislaine Valéria
authors: RV
authors: Burim
authors: Regina Helena Costa
authors: RH
authors: Queiroz
authors: Maria de Lourdes Pires
authors: Mde L
authors: Bianchi
authors: Lusânia Maria Greggi
authors: LM
authors: Antunes
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements / Q000633:toxicity*; D004317:Doxorubicin / Q000037:antagonists & inhibitors; D016158:Genes, p53 / Q000187:drug effects*; D042822:Genomic Instability / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000494:pharmacology / Q000633:toxicity*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D012436:S-Adenosylmethionine; D004317:Doxorubicin; D012435:S-Adenosylhomocysteine; D008715:Methionine; D005978:Glutathione