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Naphthalene genotoxicity: DNA adducts in primate and mouse airway explants
- Source :
- Toxicol Lett
- Publication Year :
- 2019
- Publisher :
- eScholarship, University of California, 2019.
-
Abstract
- Naphthalene (NA) is a ubiquitous environmental pollutant and possible human carcinogen that forms tumors in rodents with tissue/regional and species selectivity. This study seeks to determine whether NA is able to directly adduct DNA in an ex vivo culture system. Metabolically active lung tissue was isolated and incubated in explant culture with carbon-14 labeled NA (0, 25, 250 μM) or 1,2-naphthoquinone (NQ), followed by AMS analyses of metabolite binding to DNA. Despite relatively low metabolic bioactivation in the primate airway, dose-dependent NA-DNA adduct formation was detected. More airway adducts were detected in female mice (4.7-fold) and primates (2.1-fold) than in males of the same species. Few adducts were detected in rat airway or nasal epithelium. NQ, which is a metabolic product of NA, proved to be even more potent, with levels of adduct formation 70–80-fold higher than seen when tissues were incubated with the parent compound NA. This is the first study to demonstrate NA-DNA adduct formation at a site of carcinogenesis, the mouse lung. Adducts were also detected in non-human primate lung and with a NQ metabolite of NA. Taken together, this suggests that NA may contribute to in vivo carcinogenesis through a genotoxic mechanism.
- Subjects :
- 0301 basic medicine
Enzymologic
Male
Carcinogenesis
Environmental Science and Management
Metabolite
Naphthalenes
medicine.disease_cause
Toxicology
Gene Expression Regulation, Enzymologic
Article
Adduct
DNA Adducts
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Sex Factors
Cytochrome P-450 Enzyme System
Species Specificity
Naphthoquinone
In vivo
Toxicity Tests
medicine
Animals
Lung
Carcinogen
Cancer
Chemistry
Respiratory toxicity
DNA adducts
General Medicine
Pharmacology and Pharmaceutical Sciences
Molecular biology
Macaca mulatta
Rats
030104 developmental biology
Gene Expression Regulation
Female
030217 neurology & neurosurgery
Ex vivo
Genotoxicity
Naphthalene
Explant culture
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Toxicol Lett
- Accession number :
- edsair.doi.dedup.....9122f9d767a96dbb5f24e9787e252ade