title: Methionine concentration in the diet has a tissue-specific effect on chromosomal stability in female mice.
abstract: Inadequate nutrient intake can influence the genome. Since methionine is an essential amino acid that may influence DNA integrity due to its role in the one-carbon metabolism pathway, we were interested in whether methionine imbalance can lead to genotoxic events. Adult female Swiss mice were fed a control (0.3% dl-methionine), methionine-supplemented (2.0% DL-methionine) or methionine-deficient (0% DL-methionine) diet over a 10-week period. Chromosomal damage was assessed in peripheral blood using a micronucleus test, and DNA damage was assessed in the liver, heart and peripheral blood tissues using a comet assay. The mRNA expression of the mismatch repair genes Mlh1 and Msh2 was analyzed in the liver. The frequency of micronucleus in peripheral blood was increased by 122% in the methionine-supplemented group (p<0.05). The methionine-supplemented diet did not induce DNA damage in the heart and liver tissues, but it increased DNA damage in the peripheral blood. The methionine-deficient diet reduced basal DNA damage in liver tissue. This reduction was correlated with decreased mRNA expression of Msh2. Our results demonstrate that methionine has a tissue-specific effect because methionine-supplemented diet induced both chromosomal and DNA damage in peripheral blood while the methionine-deficient diet reduced basal DNA damage in the liver.
authors.affiliation: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: afaissa@gmail.com.
authors.forename: Alexandre Ferro
authors.initials: AF
authors.lastname: Aissa
authors.forename: Tarsila Daysy Ursula Hermogenes
authors.initials: TD
authors.lastname: Gomes
authors.forename: Mara Ribeiro
authors.initials: MR
authors.lastname: Almeida
authors.forename: Lívia Cristina
authors.initials: LC
authors.lastname: Hernandes
authors.forename: Joana D'arc Castania
authors.initials: JD
authors.lastname: Darin
authors.forename: Maria Lourdes Pires
authors.initials: ML
authors.lastname: Bianchi
authors.forename: Lusânia Maria Greggi
authors.initials: LM
authors.lastname: Antunes
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D043171:Chromosomal Instability / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008715:Methionine / Q000494:pharmacology*; D051379:Mice; D015162:Micronucleus Tests; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; D008715:Methionine; C497173:Msh2 protein, mouse; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Chromosome instability; Genotoxicity; Methionine restriction; Methionine supplementation; Mutagenicity; Nutrigenomics