Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells

Autores
López, Cristofer Martín; Ramirez, Dario; Gomez Mejiba, Sandra Esther
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Pulmonary neutrophilic inflammation (PNI) is the recruitment and activation of neutrophils in themicrovasculature with the release of myeloperoxidase (MPO) in the airways. Bystanderepithelial cells can take up MPO, where it can generate HOCl. HOCl can react with DNA,generating DNA radicals, which then decay to produce several mutagenic end-oxidationproducts, such as 8-oxo-7,8-dihydro-2´–deoxyguanosine (8-oxo-dGuo). Herein, we aimed to testwhether HOCl-induced DNA radicals precede DNA oxidation and mutagenesis in A549 humanlung epithelial cells as an in vitro model that resembles PNI. Interestingly, by trapping HOClinduced DNA radicals, the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) blocks theformation of 8-oxo-dGuo and possibly other end-oxidation products, forming DNA‒DMPOnitrone adducts. By preventing DNA oxidation, DMPO reduces the mutation of the hypoxanthinephosphoribosyl transferase (hrpt) gene, one of the genes most sensitive to oxidative damage.The transcription factor p53 is known as the master regulator of the cell response to genomicdamage. By trapping DNA radicals, DMPO also blocks the translocation of p53 to the cellnucleus, suggesting that by trapping DNA radicals with DMPO, end-oxidation products areprevented, and the cell response to genomic damage is blunted. Trapping DNA radicals to reduce the accumulation of HOCl-induced mutagenic end-oxidation products will provide newtherapeutic avenues to reduce genotoxic damage during PNI.
Fil: López, Cristofer Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
NEUTROPHILIC INFLAMMATION
DNA RADICAL
LIPOPOLYSACCHARIDE
MUTATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/291624
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/291624
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cellsLópez, Cristofer MartínRamirez, DarioGomez Mejiba, Sandra EstherNEUTROPHILIC INFLAMMATIONDNA RADICALLIPOPOLYSACCHARIDEMUTATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Pulmonary neutrophilic inflammation (PNI) is the recruitment and activation of neutrophils in themicrovasculature with the release of myeloperoxidase (MPO) in the airways. Bystanderepithelial cells can take up MPO, where it can generate HOCl. HOCl can react with DNA,generating DNA radicals, which then decay to produce several mutagenic end-oxidationproducts, such as 8-oxo-7,8-dihydro-2´–deoxyguanosine (8-oxo-dGuo). Herein, we aimed to testwhether HOCl-induced DNA radicals precede DNA oxidation and mutagenesis in A549 humanlung epithelial cells as an in vitro model that resembles PNI. Interestingly, by trapping HOClinduced DNA radicals, the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) blocks theformation of 8-oxo-dGuo and possibly other end-oxidation products, forming DNA‒DMPOnitrone adducts. By preventing DNA oxidation, DMPO reduces the mutation of the hypoxanthinephosphoribosyl transferase (hrpt) gene, one of the genes most sensitive to oxidative damage.The transcription factor p53 is known as the master regulator of the cell response to genomicdamage. By trapping DNA radicals, DMPO also blocks the translocation of p53 to the cellnucleus, suggesting that by trapping DNA radicals with DMPO, end-oxidation products areprevented, and the cell response to genomic damage is blunted. Trapping DNA radicals to reduce the accumulation of HOCl-induced mutagenic end-oxidation products will provide newtherapeutic avenues to reduce genotoxic damage during PNI.Fil: López, Cristofer Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaLandes Bioscience2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/291624López, Cristofer Martín; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells; Landes Bioscience; Oxidative Medicine and Cellular Longevity; 8868348; 9-2025; 1-151942-09001942-0994CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://doi.org/10.1155/omcl/8868348info:eu-repo/semantics/altIdentifier/doi/10.1155/omcl/8868348info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T15:40:46Zoai:ri.conicet.gov.ar:11336/291624instacron: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:34982026-08-25 15:40:46.509CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
title Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
spellingShingle Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
López, Cristofer Martín
NEUTROPHILIC INFLAMMATION
DNA RADICAL
LIPOPOLYSACCHARIDE
MUTATION
title_short Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
title_full Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
title_fullStr Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
title_full_unstemmed Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
title_sort Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells
dc.creator.none.fl_str_mv López, Cristofer Martín
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author López, Cristofer Martín
author_facet López, Cristofer Martín
Ramirez, Dario
Gomez Mejiba, Sandra Esther
author_role author
author2 Ramirez, Dario
Gomez Mejiba, Sandra Esther
author2_role author
author
dc.subject.none.fl_str_mv NEUTROPHILIC INFLAMMATION
DNA RADICAL
LIPOPOLYSACCHARIDE
MUTATION
topic NEUTROPHILIC INFLAMMATION
DNA RADICAL
LIPOPOLYSACCHARIDE
MUTATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Pulmonary neutrophilic inflammation (PNI) is the recruitment and activation of neutrophils in themicrovasculature with the release of myeloperoxidase (MPO) in the airways. Bystanderepithelial cells can take up MPO, where it can generate HOCl. HOCl can react with DNA,generating DNA radicals, which then decay to produce several mutagenic end-oxidationproducts, such as 8-oxo-7,8-dihydro-2´–deoxyguanosine (8-oxo-dGuo). Herein, we aimed to testwhether HOCl-induced DNA radicals precede DNA oxidation and mutagenesis in A549 humanlung epithelial cells as an in vitro model that resembles PNI. Interestingly, by trapping HOClinduced DNA radicals, the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) blocks theformation of 8-oxo-dGuo and possibly other end-oxidation products, forming DNA‒DMPOnitrone adducts. By preventing DNA oxidation, DMPO reduces the mutation of the hypoxanthinephosphoribosyl transferase (hrpt) gene, one of the genes most sensitive to oxidative damage.The transcription factor p53 is known as the master regulator of the cell response to genomicdamage. By trapping DNA radicals, DMPO also blocks the translocation of p53 to the cellnucleus, suggesting that by trapping DNA radicals with DMPO, end-oxidation products areprevented, and the cell response to genomic damage is blunted. Trapping DNA radicals to reduce the accumulation of HOCl-induced mutagenic end-oxidation products will provide newtherapeutic avenues to reduce genotoxic damage during PNI.
Fil: López, Cristofer Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Gomez Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description Pulmonary neutrophilic inflammation (PNI) is the recruitment and activation of neutrophils in themicrovasculature with the release of myeloperoxidase (MPO) in the airways. Bystanderepithelial cells can take up MPO, where it can generate HOCl. HOCl can react with DNA,generating DNA radicals, which then decay to produce several mutagenic end-oxidationproducts, such as 8-oxo-7,8-dihydro-2´–deoxyguanosine (8-oxo-dGuo). Herein, we aimed to testwhether HOCl-induced DNA radicals precede DNA oxidation and mutagenesis in A549 humanlung epithelial cells as an in vitro model that resembles PNI. Interestingly, by trapping HOClinduced DNA radicals, the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) blocks theformation of 8-oxo-dGuo and possibly other end-oxidation products, forming DNA‒DMPOnitrone adducts. By preventing DNA oxidation, DMPO reduces the mutation of the hypoxanthinephosphoribosyl transferase (hrpt) gene, one of the genes most sensitive to oxidative damage.The transcription factor p53 is known as the master regulator of the cell response to genomicdamage. By trapping DNA radicals, DMPO also blocks the translocation of p53 to the cellnucleus, suggesting that by trapping DNA radicals with DMPO, end-oxidation products areprevented, and the cell response to genomic damage is blunted. Trapping DNA radicals to reduce the accumulation of HOCl-induced mutagenic end-oxidation products will provide newtherapeutic avenues to reduce genotoxic damage during PNI.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
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/11336/291624
López, Cristofer Martín; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells; Landes Bioscience; Oxidative Medicine and Cellular Longevity; 8868348; 9-2025; 1-15
1942-0900
1942-0994
CONICET Digital
CONICET
url http://hdl.handle.net/11336/291624
identifier_str_mv López, Cristofer Martín; Ramirez, Dario; Gomez Mejiba, Sandra Esther; Trapping DNA radicals with DMPO reduces hypochlorous acid-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutagenesis in lung epithelial cells; Landes Bioscience; Oxidative Medicine and Cellular Longevity; 8868348; 9-2025; 1-15
1942-0900
1942-0994
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://doi.org/10.1155/omcl/8868348
info:eu-repo/semantics/altIdentifier/doi/10.1155/omcl/8868348
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Landes Bioscience
publisher.none.fl_str_mv Landes Bioscience
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 13.265058

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