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HERO ID
4715969
Reference Type
Journal Article
Title
Naphthalene DNA adduct formation and tolerance in the lung
Author(s)
Buchholz, BA; Carratt, SA; Kuhn, EA; Collette, NM; Ding, X; Van Winkle, LS
Year
2018
Is Peer Reviewed?
1
Journal
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
ISSN:
0168-583X
Volume
438
Page Numbers
119-123
Language
English
PMID
30631217
DOI
10.1016/j.nimb.2018.07.004
Web of Science Id
WOS:000453491500022
URL
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85049741385&doi=10.1016%2fj.nimb.2018.07.004&partnerID=40&md5=40174e37d371480cd5681c5e1840cb27
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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.
Keywords
naphthalene; carcinogen; DNA adducts; tolerance test
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IRIS
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Naphthalene
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Combined data set
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Mechanisms of cancer
Feb 2019 Update
WOS
January 2021 Update
PubMed
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Mouse Lung Tumor Workshop 2014
Mouse Lung Tumor Initial Search Sept-Oct 2023
PubMed
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Naphthalene (2021 Evidence mapping publication)
Database Searches
PubMed
WOS
Combined data set
Data set for title/abstract screening
Data set for full text review
Excluded – PECO criteria not met (full-text)
Supplemental material
Mechanistic
Mechanisms of cancer
Feb 2019 Update
WOS
January 2021 Update
PubMed
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