Naphthalene genotoxicity: DNA adducts in primate and mouse airway explants
- Univ. of California, Davis, CA (United States). Center for Health and the Environment
- SUNY Polytechnic Inst., Albany, NY (United States). College of Nanoscale Science and Engineering
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Univ. of California, Davis, CA (United States). Center for Health and the Environment. Dept. of Anatomy, Physiology and Cell Biology. School of Veterinary Medicine
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 here 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.
- Research Organization:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of California, Davis, CA (United States); SUNY Polytechnic Inst., Albany, NY (United States)
- Sponsoring Organization:
- USDOE National Nuclear Security Administration (NNSA); National Inst. of Health (NIH) (United States)
- Grant/Contract Number:
- AC52-07NA27344; R01 ES020867; ES020867S1; P41GM103483; P30 ES023513; DOD LC130820; P30 ES006694; ES007058
- OSTI ID:
- 1497294
- Report Number(s):
- LLNL-JRNL-739704; 893381
- Journal Information:
- Toxicology Letters, Vol. 305; ISSN 0378-4274
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
Metabolism and Lung Toxicity of Inhaled Naphthalene: Effects of Postnatal Age and Sex
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journal | April 2019 |
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