title: Micronuclei in bone marrow and liver in relation to hepatic metabolism and antioxidant response due to coexposure to chloroform, dichloromethane, and toluene in the rat model.
abstract: Genotoxicity in cells may occur in different ways, direct interaction, production of electrophilic metabolites, and secondary genotoxicity via oxidative stress. Chloroform, dichloromethane, and toluene are primarily metabolized in liver by CYP2E1, producing reactive electrophilic metabolites, and may also produce oxidative stress via the uncoupled CYP2E1 catalytic cycle. Additionally, GSTT1 also participates in dichloromethane activation. Despite the oxidative metabolism of these compounds and the production of oxidative adducts, their genotoxicity in the bone marrow micronucleus test is unclear. The objective of this work was to analyze whether the oxidative metabolism induced by the coexposure to these compounds would account for increased micronucleus frequency. We used an approach including the analysis of phase I, phase II, and antioxidant enzymes, oxidative stress biomarkers, and micronuclei in bone marrow (MNPCE) and hepatocytes (MNHEP). Rats were administered different doses of an artificial mixture of CLF/DCM/TOL, under two regimes. After one administration MNPCE frequency increased in correlation with induced GSTT1 activity and no oxidative stress occurred. Conversely, after three-day treatments oxidative stress was observed, without genotoxicity. The effects observed indicate that MNPCE by the coexposure to these VOCs could be increased via inducing the activity of metabolism enzymes.
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, 04510 México, DF, Mexico ; Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Tlalpan, 14080 México, DF, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Belmont-Díaz
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, 04510 México, DF, Mexico.
authors.forename: Ana Paulina
authors.initials: AP
authors.lastname: López-Gordillo
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, 04510 México, DF, Mexico.
authors.forename: Eunice
authors.initials: E
authors.lastname: Molina Garduño
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, 04510 México, DF, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Serrano-García
authors.affiliation: Laboratorio de Neuroquímica, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, 04530 México, DF, Mexico.
authors.forename: Elvia
authors.initials: E
authors.lastname: Coballase-Urrutia
authors.affiliation: Laboratorio de Neuroquímica, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, 04530 México, DF, Mexico.
authors.forename: Noemí
authors.initials: N
authors.lastname: Cárdenas-Rodríguez
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, 04510 México, DF, Mexico.
authors.forename: Omar
authors.initials: O
authors.lastname: Arellano-Aguilar
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, 04510 México, DF, Mexico.
authors.forename: Regina D
authors.initials: RD
authors.lastname: Montero-Montoya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D002725:Chloroform / Q000633:toxicity; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000187:drug effects*; D008752:Methylene Chloride / Q000633:toxicity; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D014050:Toluene / Q000633:toxicity
chemical_list: D000975:Antioxidants; D014050:Toluene; D008752:Methylene Chloride; D002725:Chloroform; D019392:Cytochrome P-450 CYP2E1; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase