Title: Naphthalene genotoxicity: DNA adducts in primate and mouse airway explants.
Authors: Carratt, Sarah A; Hartog, Matthew; Buchholz, Bruce A; Kuhn, Edward A; Collette, Nicole M; Ding, Xinxin; Van Winkle, Laura S
Published In Toxicol Lett, (2019 May 01)
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.
PubMed ID: 30684585
MeSH Terms: Animals; Carcinogenesis; Cytochrome P-450 Enzyme System/genetics; Cytochrome P-450 Enzyme System/metabolism; DNA Adducts; Female; Gene Expression Regulation, Enzymologic/drug effects; Lung/drug effects*; Lung/metabolism; Macaca mulatta; Male; Mice; Naphthalenes/toxicity*; Rats; Sex Factors; Species Specificity; Toxicity Tests