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 noelia.ramirez@urv.cat maria.vinaixa@urv.cat carlamelissa.merino@estudiants.urv.cat carlamelissa.merino@estudiants.urv.cat
Author identifier: 0000-0001-9804-0171 0000-0001-9804-0171
Record's date: 2023-02-19
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: http://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
Repositori URV