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Título : Modulation of rat liver citochrome P450 by protein restriction assessed by biochemical and bacterial mutagenicity methods
Creador: Cancino Badías L
Nivel de acceso: Open access
Palabras clave : Biotransformación - Efectos de drogas
Carcinógenos - farmacocinética
Dieta restringida en proteinas
Proteínas en la Dieta - farmacología
Microsomas Hepáticos - efectos de drogas
Pruebas de Mutagenicidad
Mutágenos - farmacocinética
Biotransformation - drug effects
Carcinogens - pharmacokinetics
Diet, Protein-Restricted
Dietary Proteins - pharmacology
Microsomes, Liver - Drug effects
Mutagenicity Tests
Mutagens - pharmacokinetics
Descripción : Protein restriction (PR) significantly inhibits spontaneous and chemical carcinogenesis. Several factors seem to be involved in this effect, including a decrease in body weight, cellular proliferation and DNA damage and an increase in antioxidant defenses. The current study was designed to determine modifications in some hepatic cytochromes P450 (CYPs) due to a hypoproteic diet and to investigate its implications on chemical mutagenesis. Western blot analysis showed decreases of 73, 40 and 74% in CYP1A, CYP2B and CYP2E1 protein concentrations in hepatic microsomes from animals fed a protein-restricted (6% protein) diet for 6 weeks in comparison with microsomes from rats fed a 24% protein diet during the same period. In the same way, low protein fed animals showed a 3.5-fold decrease in hepatic CYP1A1-associated ethoxyresorufin O-deethylase activity, a 6-fold decrease in CYP1A2-associated methoxyresorufin O-demethylase activity, a 1.7-fold decrease in CYP2B1-associated penthoxyresorufin O-dealkylase activity, a 9-fold decrease in CYP2B2-associated benzyloxyresorufin O-dealkylase and, finally, a 3.4-fold decrease in CYP2E1-associated 4-nitrophenol hydroxylase activity. As a result of decreased CYP hepatic protein concentrations and enzymatic activities, liver S9 from rats fed a hypoproteic diet was less efficient in activating promutagens than S9 prepared from rats fed a 24% protein diet in the Ames test. Mutagenic potency obtained with protein-restricted S9 was reduced 25-fold for 2-aminoanthracene, 1.5-fold for N-nitrosodipropylamine, 12.5-fold for N-nitrosodibutylamine, 2-fold for cyclophosphamide and N-nitrosopyrrolidine and 71-fold for N-nitrosodimethylamine. However, the mutagenic potency of benzo[a]pyrene was the same (4 revertants/μg) with S9 derived from rats fed either a 6 or 24% protein diet.
Colaborador(es) u otros Autores: Reyes RE
Nosti R
Pérez I
Dorado V
Caballero S
Soria A
Camacho Carranza R
Escobar D
Espinosa Aguirre JJ
Fecha de publicación : 2003
Tipo de publicación: Artículo
Formato: pdf
Identificador del Recurso : 10.1093/mutage/18.1.95
Fuente: Mutagenesis 18(1):95 - 100
URI : http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2601
Idioma: eng
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