title: Tissue-specific induction of the carcinogen-inducible cytochrome P450 isoforms in the gastrointestinal tract.
abstract: Gastrointestinal tissues are directly exposed to dietary xenobiotics. In spite of this, modulation of cytochrome P450 (CYP) enzymes in the gastrointestinal tract is not well established. CYP induction could facilitate transformation of chemical agents to potentially toxic or carcinogenic metabolites. This might also determine drug efficacy, burden of foreign chemicals on tissues or bioavailability of certain therapeutic agents. In order to assess the induction of the CYP subfamilies 1A1/2, 2B1/2, 2E1 and 3A2 in the gastrointestinal tract, male Wistar rats were treated with phenobarbital/β-naphthoflavone (PB/NF), cyclohexanol/albendazole (CH/ABZ) or toluene (TL). Microsomal fractions were prepared from tissue samples of the esophagus, the stomach, the duodenum, the colon and the liver. Western blot and enzymatic activity analyses revealed an increase in the expression and activity of CYP1A1/2 and CYP3A2 isoenzymes in the esophageal, duodenal and colonic microsomes from animals treated with PB/NF. CYP1A1/2 and CYP3A2 were induced in hepatic and duodenum microsomes by treatment with CH/ABZ. Our results demonstrate differential induction of CYP along the gastrointestinal tract by known CYP hepatic inducers, being the treatment with PB/NF the best induction system of the CYPs.
authors.affiliation: Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría (INP), Insurgentes Sur, 3700-C, 04530 México, DF., Mexico.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hernández-Martínez
authors.forename: Heriberto
authors.initials: H
authors.lastname: Caballero-Ortega
authors.forename: Víctor
authors.initials: V
authors.lastname: Dorado-González
authors.forename: Norma
authors.initials: N
authors.lastname: Labra-Ruiz
authors.forename: Jesús Javier
authors.initials: JJ
authors.lastname: Espinosa-Aguirre
authors.forename: Josefina
authors.initials: J
authors.lastname: Gómez-Garduño
authors.forename: Araceli
authors.initials: A
authors.lastname: Vences-Mejía