Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-10-9
pubmed:abstractText
A procedure has been developed for estimating the survival time of short-lived alkylating agents in a flow system at physiological temperature and pH. The system simulated the slow release into the bloodstream of a reactive compound formed in the liver. A solution of the reactive compound was injected slowly into a fast stream of aqueous fluid and immediately mixed. After a delay (up to 1 min) determined by a length of tube, during which hydrolysis took place, the surviving reactive compound was trapped on a column of immobilized thiol (thiol-Sepharose), and the fluid was recirculated via a reservoir. The system was used to study the hydrolysis of the pyrrolizidine alkaloid metabolites dehydromonocrotaline, dehydro-anacrotine and dehydroretrorsine. The S-bound pyrrolic moiety in the trap was measured colorimetrically and hydrolysis rates were estimated after a series of 1-h runs with different delay times. Hydrolysis of dehydroretrorsine was very rapid, whereas the hydrolysis of dehydromonocrotaline and dehydro-anacrotine fitted biphasic first-order reactions, with a faster first phase. By isolating and identifying the trapped products from dehydromoncrotaline it was shown that the two phases involved hydrolysis of the 7- and 9-ester groups, respectively. The results supported the view that a proportion of the reactive metabolites from the alkaloids monocrotaline and anacrotine would be able to survive long enough to be transported from the liver to the lungs of a rat. The flow system would be applicable to the study of other types of short-lived metabolites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0009-2797
pubmed:author
pubmed:issnType
Print
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-30
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Trapping and measurement of short-lived alkylating agents in a recirculating flow system.
pubmed:affiliation
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, U.K.
pubmed:publicationType
Journal Article