Linked Life Data

20974116

Source:http://linkedlifedata.com/resource/pubmed/id/20974116

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2011-6-6
pubmed:abstractText
1,3-Butadiene (BD) is a known rodent and human carcinogen that is metabolized mainly by P450 2E1 to three epoxides, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB) and 1,2-epoxy-3,4-butanediol (EB-diol). The individual epoxides vary up to 200-fold in their mutagenic potency, with DEB being the most mutagenic metabolite. It is important to understand the internal formation of the individual epoxides to assign the relative risk for each metabolite and to understand the molecular mechanisms responsible for major species differences in carcinogenicity. We have conducted extensive exposure-biomarker studies on mice, rats and humans. Using low exposures that range from current occupational levels to human exposures from tobacco smoke has provided evidence that mice are very different from humans, with mice forming ?200 times more DEB than humans at exposures of 0.1-1.5ppm BD. While no gender differences have been noted in mice and rats for globin adducts or N-7 guanine adducts, female rats and mice had 2-3-fold higher Hprt mutations and DNA-DNA cross-links, suggesting a gender difference in DNA repair. Numerous molecular epidemiology studies have evaluated globin adducts and Hprt mutations, SCEs and chromosomal abnormalities. None of the blinded studies have shown evidence of human genotoxicity at current occupational exposures and studies of globin adducts have shown similar or lower formation of adducts in females than males. If one calculates the EB dose-equivalents for the three species, mice clearly differ from rats and humans, being ?44 and 174 times greater than rats and humans, respectively. These data provide a scientific basis for improved risk assessment of BD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1872-7786
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
192
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
150-4
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
1,3-Butadiene: Biomarkers and application to risk assessment.
pubmed:affiliation
Department of Environmental Sciences and Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27559, USA. james_swenberg@unc.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural