title: Moderate malnutrition in rats induces somatic gene mutations.
abstract: The relationship between malnutrition and genetic damage has been widely studied in human and animal models, leading to the observation that interactions between genotoxic exposure and micronutrient status appear to affect genomic stability. A new assay has been developed that uses the phosphatidylinositol glycan class A gene (Pig-a) as a reporter for measuring in vivo gene mutation. The Pig-a assay can be employed to evaluate mutant frequencies (MFs) in peripheral blood reticulocytes (RETs) and erythrocytes (RBCs) using flow cytometry. In the present study, we assessed the effects of malnutrition on mutagenic susceptibility by exposing undernourished (UN) and well-nourished (WN) rats to N-ethyl-N-nitrosourea (ENU) and measuring Pig-a MFs. Two week-old UN and WN male Han-Wistar rats were treated daily with 0, 20, or 40mg/kg ENU for 3 consecutive days. Blood was collected from the tail vein one day before ENU treatment (Day-1) and after ENU administration on Days 7, 14, 21, 28, 35, 42, 49, 56 and 63. Pig-a MFs were measured in RETs and RBCs as the RET(CD59-) and RBC(CD59-) frequencies. In the vehicle control groups, the frequencies of mutant RETs and RBCs were significantly higher in UN rats compared with WN rats at all sampling times. The ENU treatments increased RET and RBC MFs starting at Day 7. Although ENU-induced Pig-a MFs were consistently lower in UN rats than in WN rats, these differences were not significant. To understand these responses, further studies should use other mutagens and nucleated surrogate cells and examine the types of mutations induced in UN and WN rats.
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Avenida San Rafael Atlixco 186, C.P. 09340 México D.F., México; Doctorado en Biología Experimental, Universidad Autónoma Metropolitana, Avenida San Rafael Atlixco 186, C.P. 09340 México, D.F., México. Electronic address: mon.pach13@gmail.com.
authors.forename: M Monserrat
authors.initials: MM
authors.lastname: Pacheco-Martínez
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Avenida San Rafael Atlixco 186, C.P. 09340 México D.F., México. Electronic address: cobe@xanum.uam.mx.
authors.forename: Edith
authors.initials: E
authors.lastname: Cortés-Barberena
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Avenida San Rafael Atlixco 186, C.P. 09340 México D.F., México. Electronic address: elsi_cervantes@hotmail.com.
authors.forename: Elsa
authors.initials: E
authors.lastname: Cervantes-Ríos
authors.affiliation: Unidad de Investigación en Genética y Toxicología Ambiental, Facultad de Estudios Superiores-Zaragoza, UNAM, A.P. 9-020, México D.F., México. Electronic address: carmen.garcia@unam.mx.
authors.forename: María
authors.initials: M
authors.lastname: Del Carmen García-Rodríguez
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Avenida San Rafael Atlixco 186, C.P. 09340 México D.F., México. Electronic address: leor@xanum.uam.mx.
authors.forename: Leonor
authors.initials: L
authors.lastname: Rodríguez-Cruz
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Avenida San Rafael Atlixco 186, C.P. 09340 México D.F., México. Electronic address: arom@xanum.uam.mx.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ortiz-Muñiz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004249:DNA Damage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005038:Ethylnitrosourea / Q000633:toxicity; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D059645:Mutation Rate; D017208:Rats, Wistar; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; D005038:Ethylnitrosourea
keywords: Erythrocytes; Malnutrition; Mutagenesis; Pig-a assay; Reticulocytes