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Toxicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in early development: A wide-scope metabolomics assay in zebrafish embryos

  • Identification data

    Identifier: imarina:9244259
    Authors:
    Merino CCasado MPiña BVinaixa MRamírez N
    Abstract:
    The tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant for which toxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies. Embryos exposed to different NNK concentrations were monitored for lethality and for the appearance of malformations during the first five days after fertilization. LC-MS based untargeted metabolomics was subsequently performed for a wide-scope assay of NNK-related metabolic alterations. Our results revealed the presence of not only the parental compound, but also of two known NNK metabolites, 4-Hydroxy-4-(3-pyridyl)-butyric acid (HPBA) and 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide) in exposed embryos likely resulting from active CYP450-mediated α-hydroxylation and NNK detoxification pathways, respectively. This was paralleled by a disruption in purine and pyrimidine metabolisms and the activation of the base excision repair pathway. Our results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.
  • Others:

    Author, as appears in the article.: Merino C; Casado M; Piña B; Vinaixa M; Ramírez N
    Department: Enginyeria Electrònica, Elèctrica i Automàtica
    URV's Author/s: Merino Ruiz, Carla Melissa / Ramírez González, Noelia / Vinaixa Crevillent, Maria
    Keywords: Tobacco-specific nitrosamine Nucleotide metabolism Metabolomics Early development Danio rerio 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (nnk) 4-(methylnitrosamino)-1-(3-pyridyl)-1- tumorigenicity toxicology thirdhand-smoke nucleotide metabolism metabolomics metabolism lung in-vivo exposure early development dna adduct formation danio rerio carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone butanone (nnk)
    Abstract: The tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant for which toxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies. Embryos exposed to different NNK concentrations were monitored for lethality and for the appearance of malformations during the first five days after fertilization. LC-MS based untargeted metabolomics was subsequently performed for a wide-scope assay of NNK-related metabolic alterations. Our results revealed the presence of not only the parental compound, but also of two known NNK metabolites, 4-Hydroxy-4-(3-pyridyl)-butyric acid (HPBA) and 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide) in exposed embryos likely resulting from active CYP450-mediated α-hydroxylation and NNK detoxification pathways, respectively. This was paralleled by a disruption in purine and pyrimidine metabolisms and the activation of the base excision repair pathway. Our results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.
    Thematic Areas: Zootecnia / recursos pesqueiros Waste management and disposal Química Pollution Odontología Medicina ii Materiais Interdisciplinar Health, toxicology and mutagenesis Geografía Geociências General o multidisciplinar Farmacia Environmental sciences Environmental engineering Environmental chemistry Ensino Engineering, environmental Engineering, civil Engenharias iv Engenharias iii Engenharias ii Engenharias i Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Biotecnología Biodiversidade Astronomia / física
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: maria.vinaixa@urv.cat carlamelissa.merino@estudiants.urv.cat carlamelissa.merino@estudiants.urv.cat maria.vinaixa@urv.cat
    Author identifier: 0000-0001-9804-0171 0000-0001-9804-0171
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.sciencedirect.com/science/article/pii/S0304389421027151?via%3Dihub
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Journal Of Hazardous Materials. 429 127746-
    APA: Merino C; Casado M; Piña B; Vinaixa M; Ramírez N (2022). Toxicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in early development: A wide-scope metabolomics assay in zebrafish embryos. Journal Of Hazardous Materials, 429(), 127746-. DOI: 10.1016/j.jhazmat.2021.127746
    Article's DOI: 10.1016/j.jhazmat.2021.127746
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2022
    Publication Type: Journal Publications
  • Keywords:

    Engineering, Civil,Engineering, Environmental,Environmental Chemistry,Environmental Engineering,Environmental Sciences,Health, Toxicology and Mutagenesis,Pollution,Waste Management and Disposal
    Tobacco-specific nitrosamine
    Nucleotide metabolism
    Metabolomics
    Early development
    Danio rerio
    4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (nnk)
    4-(methylnitrosamino)-1-(3-pyridyl)-1-
    tumorigenicity
    toxicology
    thirdhand-smoke
    nucleotide metabolism
    metabolomics
    metabolism
    lung
    in-vivo
    exposure
    early development
    dna adduct formation
    danio rerio
    carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
    butanone (nnk)
    Zootecnia / recursos pesqueiros
    Waste management and disposal
    Química
    Pollution
    Odontología
    Medicina ii
    Materiais
    Interdisciplinar
    Health, toxicology and mutagenesis
    Geografía
    Geociências
    General o multidisciplinar
    Farmacia
    Environmental sciences
    Environmental engineering
    Environmental chemistry
    Ensino
    Engineering, environmental
    Engineering, civil
    Engenharias iv
    Engenharias iii
    Engenharias ii
    Engenharias i
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Ciência da computação
    Biotecnología
    Biodiversidade
    Astronomia / física
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