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HERO ID
1039241
Reference Type
Journal Article
Title
Formation of hydroxymethyl DNA adducts in rats orally exposed to stable isotope labeled methanol
Author(s)
Lu, K; Gul, H; Upton, PB; Moeller, BC; Swenberg, JA
Year
2012
Is Peer Reviewed?
1
Journal
Toxicological Sciences
ISSN:
1096-6080
EISSN:
1096-0929
Volume
126
Issue
1
Page Numbers
28-38
Language
English
PMID
22157354
DOI
10.1093/toxsci/kfr328
Web of Science Id
WOS:000300989300004
URL
http://
://WOS:000300989300004
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Abstract
Methanol is a large volume industrial chemical and widely used solvent and fuel additive. Methanol's well known toxicity and use in a wide spectrum of applications has raised long-standing environmental issues over its safety, including its carcinogenicity. Methanol has not been listed as a carcinogen by any regulatory agency; however, there are debates about its carcinogenic potential. Formaldehyde, a metabolite of methanol, has been proposed to be responsible for the carcinogenesis of methanol. Formaldehyde is a known carcinogen and actively targets DNA and protein, causing diverse DNA and protein damage. However, formaldehyde-induced DNA adducts arising from the metabolism of methanol have not been reported previously, largely due to the absence of suitable DNA biomarkers and the inability to differentiate what was due to methanol compared with the substantial background of endogenous formaldehyde. Recently, we developed a unique approach combining highly sensitive liquid chromatography-mass spectrometry methods and exposure to stable isotope labeled chemicals to simultaneously quantify formaldehyde-specific endogenous and exogenous DNA adducts. In this study, rats were exposed daily to 500 or 2000 mg/kg [(13)CD(4)]-methanol by gavage for 5 days. Our data demonstrate that labeled formaldehyde arising from [(13)CD(4)]-methanol induced hydroxymethyl DNA adducts in multiple tissues in a dose-dependent manner. The results also demonstrated that the number of exogenous DNA adducts was lower than the number of endogenous hydroxymethyl DNA adducts in all tissues of rats administered 500 mg/kg per day for 5 days, a lethal dose to humans, even after incorporating an average factor of 4 for reduced metabolism due to isotope effects of deuterium-labeled methanol into account.
Keywords
DNA adducts; genetic toxicology; formaldehyde; methanol; hydroxymethyl adducts; mass spectrometry
Tags
IRIS
•
Formaldehyde
Exposure Litsearch Jan 2012 - Aug 2015
PubMed
Human exposure to formaldehyde
Prior to 2013 Search
Nervous system effects
Found
Database search results
Web of Science
Screened
Title/abstract
Specific to other chemicals
Toxicokinetics
Cited
Genotoxicity
Cited in text
Retroactive RIS import
Pre2013
Merged Litsearch Results 100912
Merged LitSearch Results ToxNet 101012
Merged LitSearch Additions 86 Reviews SCREEN
Web of Science Search 100412
2013
HCHON tox Ref Identification 022713
•
Methanol (Non-Cancer)
Cited in Final (2013)
Cited in External Review Draft (2013)
Search 2012
WOS
ToxNet
ProQuest
Search Jan 30 2013
WOS
ToxNet
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