Naphthalene genotoxicity: DNA adducts in primate and mouse airway explants. (1st May 2019)

• Record Type: Journal Article
• Authors: Carratt, Sarah A.; Hartog, Matthew; Buchholz, Bruce A.; Kuhn, Edward A.; Collette, Nicole M.; Ding, Xinxin; Van Winkle, Laura S.
• Is Part Of: Toxicology letters. Volume 305(2019)
• Page Start: 103
• Page End: 109
• Publication Date: 2019-05-01
• Subjects: Naphthalene -- Naphthoquinone -- DNA adducts -- Respiratory toxicity; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.01.009
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Naphthalene DNA adducts were detected in primate and mouse airways. Female mouse (4.7-fold) and primate (2.1-fold) airway adducts exceeded male levels. Few naphthalene DNA adducts were detected in rat airway or nasal epithelium. Naphthoquinone DNA adducts were 70 to 80-fold higher than naphthalene DNA adducts. 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.