Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions

Autores
Bartel, Laura Cecilia; Montalto, Maria; Castro, Jose Alberto
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Several nitrofurans and nitroimidazoles have been widely used in veterinary medicine. Some of these compounds are breast carcinogens in rodents and their mechanism of action is hypothesized to be related to reactive metabolites generated by nitroreduction and/or via oxygen-dependent redox cycling. The present work describes the nitroreductive metabolism of nitrofurazone, nitrofurantoin, furazolidone, and metronidazole by the cytosolic and microsomal fractions of mammary tissue from female Sprague-Dawley rats. The data obtained were compared with those obtained with nifurtimox and benznidazole, two well-known rodent carcinogen/mutagens nitroheterocycles. The nitroreductase activity of pure milk xanthine-oxidoreductase (XOR) was evaluated for screening purposes. All the nitrofurans were nitroreduced either by the pure XOR or the cytosolic fraction in the presence of hypoxanthine, and these activities were inhibited by allopurinol. Furthermore, they were nitroreduced by the microsomal fraction in the presence of NADPH, except for the nitrofurazone, suggesting the participation of cytochrome P450 reductase. Nitrofurans metabolism was significantly more intense than that of NFX. No equivalent nitroreductase activity was observed in either subcellular fraction using nitroimidazolic compounds as substrates. These results suggest that the nitroreductive metabolism of nitrofurans and the subsequent redox cycling might be involved in the associated mammary tissue carcinogenic effects.
Fil: Bartel, Laura Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Materia
Carcinogenicity
Mammary Tissue
Nitrofurans
Nitroimidazoles
Xanthine-Oxidoreductase
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/82109
Acceder
id CONICETDig_62ea9e26cc96d84533df501002e1fff3
oai_identifier_str oai:ri.conicet.gov.ar:11336/82109
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractionsBartel, Laura CeciliaMontalto, MariaCastro, Jose AlbertoCarcinogenicityMammary TissueNitrofuransNitroimidazolesXanthine-Oxidoreductasehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Several nitrofurans and nitroimidazoles have been widely used in veterinary medicine. Some of these compounds are breast carcinogens in rodents and their mechanism of action is hypothesized to be related to reactive metabolites generated by nitroreduction and/or via oxygen-dependent redox cycling. The present work describes the nitroreductive metabolism of nitrofurazone, nitrofurantoin, furazolidone, and metronidazole by the cytosolic and microsomal fractions of mammary tissue from female Sprague-Dawley rats. The data obtained were compared with those obtained with nifurtimox and benznidazole, two well-known rodent carcinogen/mutagens nitroheterocycles. The nitroreductase activity of pure milk xanthine-oxidoreductase (XOR) was evaluated for screening purposes. All the nitrofurans were nitroreduced either by the pure XOR or the cytosolic fraction in the presence of hypoxanthine, and these activities were inhibited by allopurinol. Furthermore, they were nitroreduced by the microsomal fraction in the presence of NADPH, except for the nitrofurazone, suggesting the participation of cytochrome P450 reductase. Nitrofurans metabolism was significantly more intense than that of NFX. No equivalent nitroreductase activity was observed in either subcellular fraction using nitroimidazolic compounds as substrates. These results suggest that the nitroreductive metabolism of nitrofurans and the subsequent redox cycling might be involved in the associated mammary tissue carcinogenic effects.Fil: Bartel, Laura Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaPergamon-Elsevier Science Ltd2009-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/82109Bartel, Laura Cecilia; Montalto, Maria; Castro, Jose Alberto; Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions; Pergamon-Elsevier Science Ltd; Food And Chemical Toxicology; 47; 1; 1-2009; 140-1440278-6915CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0278691508006091info:eu-repo/semantics/altIdentifier/doi/10.1016/j.fct.2008.09.069info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-31T15:21:13Zoai:ri.conicet.gov.ar:11336/82109instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-03-31 15:21:13.576CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
title Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
spellingShingle Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
Bartel, Laura Cecilia
Carcinogenicity
Mammary Tissue
Nitrofurans
Nitroimidazoles
Xanthine-Oxidoreductase
title_short Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
title_full Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
title_fullStr Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
title_full_unstemmed Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
title_sort Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions
dc.creator.none.fl_str_mv Bartel, Laura Cecilia
Montalto, Maria
Castro, Jose Alberto
author Bartel, Laura Cecilia
author_facet Bartel, Laura Cecilia
Montalto, Maria
Castro, Jose Alberto
author_role author
author2 Montalto, Maria
Castro, Jose Alberto
author2_role author
author
dc.subject.none.fl_str_mv Carcinogenicity
Mammary Tissue
Nitrofurans
Nitroimidazoles
Xanthine-Oxidoreductase
topic Carcinogenicity
Mammary Tissue
Nitrofurans
Nitroimidazoles
Xanthine-Oxidoreductase
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Several nitrofurans and nitroimidazoles have been widely used in veterinary medicine. Some of these compounds are breast carcinogens in rodents and their mechanism of action is hypothesized to be related to reactive metabolites generated by nitroreduction and/or via oxygen-dependent redox cycling. The present work describes the nitroreductive metabolism of nitrofurazone, nitrofurantoin, furazolidone, and metronidazole by the cytosolic and microsomal fractions of mammary tissue from female Sprague-Dawley rats. The data obtained were compared with those obtained with nifurtimox and benznidazole, two well-known rodent carcinogen/mutagens nitroheterocycles. The nitroreductase activity of pure milk xanthine-oxidoreductase (XOR) was evaluated for screening purposes. All the nitrofurans were nitroreduced either by the pure XOR or the cytosolic fraction in the presence of hypoxanthine, and these activities were inhibited by allopurinol. Furthermore, they were nitroreduced by the microsomal fraction in the presence of NADPH, except for the nitrofurazone, suggesting the participation of cytochrome P450 reductase. Nitrofurans metabolism was significantly more intense than that of NFX. No equivalent nitroreductase activity was observed in either subcellular fraction using nitroimidazolic compounds as substrates. These results suggest that the nitroreductive metabolism of nitrofurans and the subsequent redox cycling might be involved in the associated mammary tissue carcinogenic effects.
Fil: Bartel, Laura Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
description Several nitrofurans and nitroimidazoles have been widely used in veterinary medicine. Some of these compounds are breast carcinogens in rodents and their mechanism of action is hypothesized to be related to reactive metabolites generated by nitroreduction and/or via oxygen-dependent redox cycling. The present work describes the nitroreductive metabolism of nitrofurazone, nitrofurantoin, furazolidone, and metronidazole by the cytosolic and microsomal fractions of mammary tissue from female Sprague-Dawley rats. The data obtained were compared with those obtained with nifurtimox and benznidazole, two well-known rodent carcinogen/mutagens nitroheterocycles. The nitroreductase activity of pure milk xanthine-oxidoreductase (XOR) was evaluated for screening purposes. All the nitrofurans were nitroreduced either by the pure XOR or the cytosolic fraction in the presence of hypoxanthine, and these activities were inhibited by allopurinol. Furthermore, they were nitroreduced by the microsomal fraction in the presence of NADPH, except for the nitrofurazone, suggesting the participation of cytochrome P450 reductase. Nitrofurans metabolism was significantly more intense than that of NFX. No equivalent nitroreductase activity was observed in either subcellular fraction using nitroimidazolic compounds as substrates. These results suggest that the nitroreductive metabolism of nitrofurans and the subsequent redox cycling might be involved in the associated mammary tissue carcinogenic effects.
publishDate 2009
dc.date.none.fl_str_mv 2009-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/82109
Bartel, Laura Cecilia; Montalto, Maria; Castro, Jose Alberto; Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions; Pergamon-Elsevier Science Ltd; Food And Chemical Toxicology; 47; 1; 1-2009; 140-144
0278-6915
CONICET Digital
CONICET
url http://hdl.handle.net/11336/82109
identifier_str_mv Bartel, Laura Cecilia; Montalto, Maria; Castro, Jose Alberto; Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions; Pergamon-Elsevier Science Ltd; Food And Chemical Toxicology; 47; 1; 1-2009; 140-144
0278-6915
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0278691508006091
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.fct.2008.09.069
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.822162

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