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Title: Naphthalene genotoxicity: DNA adducts in primate and mouse airway explants

Journal Article · · Toxicology Letters
 [1];  [2];  [3];  [3];  [3];  [2];  [4]
  1. Univ. of California, Davis, CA (United States). Center for Health and the Environment
  2. SUNY Polytechnic Inst., Albany, NY (United States). College of Nanoscale Science and Engineering
  3. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  4. Univ. of California, Davis, CA (United States). Center for Health and the Environment. Dept. of Anatomy, Physiology and Cell Biology. School of Veterinary Medicine
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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); SUNY Polytechnic Inst., Albany, NY (United States); Univ. of California, Davis, CA (United States)
Sponsoring Organization:
National Inst. of Health (NIH) (United States); USDOE National Nuclear Security Administration (NNSA)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1497294
Report Number(s):
LLNL-JRNL--739704; 893381
Journal Information:
Toxicology Letters, Journal Name: Toxicology Letters Vol. 305; ISSN 0378-4274
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Metabolism and Lung Toxicity of Inhaled Naphthalene: Effects of Postnatal Age and Sex journal April 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DNA adducts
naphthalene
naphthoquinone
respiratory toxicity