Naphthalene DNA adduct formation and tolerance in the lung

Bruce A. Buchholz, Sarah A. Carratt, Edward A. Kuhn, Nicole M. Collette, Xinxin Ding, Laura S. Van Winkle

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Naphthalene (NA) is a respiratory toxicant and possible human carcinogen. NA is a ubiquitous combustion product and significant component of jet fuel. The National Toxicology Program found that NA forms tumors in two species, in rats (nose) and mice (lung). However, it has been argued that NA does not pose a cancer risk to humans because NA is bioactivated by cytochrome P450 monooxygenase enzymes that have very high efficiency in the lung tissue of rodents but low efficiency in the lung tissue of humans. It is thought that NA carcinogenesis in rodents is related to repeated cycles of lung epithelial injury and repair, an indirect mechanism. Repeated in vivo exposure to NA leads to development of tolerance, with the emergence of cells more resistant to NA insult. We tested the hypothesis that tolerance involves reduced susceptibility to the formation of NA-DNA adducts. NA-DNA adduct formation in tolerant mice was examined in individual, metabolically-active mouse airways exposed ex vivo to 250 μM 14C-NA. Ex vivo dosing was used since it had been done previously and the act of creating a radioactive aerosol of a potential carcinogen posed too many safety and regulatory obstacles. Following extensive rinsing to remove unbound 14C-NA, DNA was extracted and 14C-NA-DNA adducts were quantified by accelerator mass spectrometry (AMS). The tolerant mice appeared to have slightly lower NA-DNA adduct levels than non-tolerant controls, but intra-group variations were large and the difference was statistically insignificant. It appears the tolerance may be more related to other mechanisms, such as NA-protein interactions in the airway, than DNA-adduct formation.

Original languageEnglish (US)
Pages (from-to)119-123
Number of pages5
JournalNuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms
Volume438
DOIs
StatePublished - Jan 1 2019

Keywords

  • Carcinogen
  • DNA adducts
  • Naphthalene
  • Tolerance test

ASJC Scopus subject areas

  • Nuclear and High Energy Physics
  • Instrumentation

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