Linked Life Data

10076537

Source:http://linkedlifedata.com/resource/pubmed/id/10076537

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1999-3-30
pubmed:abstractText
The metabolism and pharmacokinetics of vinyl chloride (VC) have been extensively studied in rodents and humans, but the maximum velocity (Vmax) and Michaelis constant (K(m)) for the activation of VC by microsomal monooxygenases in vitro have not yet been determined. Using a new sensitive assay, the epoxidation of VC by rat liver microsomes (adult Sprague-Dawley) at concentrations from 1 ppm to 10(6) ppm in the gas phase was measured. In the assay, the reactive VC metabolites chloroethylene oxide and 2-chloroacetaldehyde were trapped with excess cAMP, yielding, 1,N6-etheno-cAMP (epsilon cAMP) which was quantitated by HPLC fluorimetry. The trapping efficiency of electrophilic VC metabolites by cAMP was close to 10%. The specificity of the method was confirmed by purification of epsilon cAMP on an immunogel. The VC concentration in the gas phase was measured by GC/flame ionization detection, while in the aqueous phase it was calculated from the partition coefficient between air and the microsomal suspension. Activation of VC by rat liver microsomes followed Michaelis-Menten kinetics with K(m) = 7.42 +/- 0.37 (+/- SD) microM and Vmax = 4674 +/- 46 pmol.mg protein-1.min-1. Inhibitor studies and immunoinhibition assays showed that VC was activated by cytochrome P450 (CYP) 2E1 down to 1 ppm in the air phase. Based on the metabolic parameters determined, the uptake of VC by rats in vivo can be accurately predicted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1445-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Metabolic activation of vinyl chloride by rat liver microsomes: low-dose kinetics and involvement of cytochrome P450 2E1.
pubmed:affiliation
International Agency for Research on Cancer, Unit of Gene-Environment Interactions, Lyon, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't