Linked Life Data

14742322

Source:http://linkedlifedata.com/resource/pubmed/id/14742322

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-5-26
pubmed:abstractText
The food-derived, heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is genotoxic and is carcinogenic in experimental animals. Studies on the role of PhIP in human diet-related cancer would be aided considerably by the availability of a readily applicable biomarker of the internal dose of the ultimate genotoxic species. PhIP has been shown to adduct primarily at C-8 of deoxyguanosine in DNA and so the DNA repair product N(2)-(2'-deoxyguanosin-8-yl)PhIP is a potential biomarker of DNA adduction and repair after exposure to PhIP. An assay for N(2)-(2'-deoxyguanosin-8-yl)PhIP in urine has been developed based on liquid chromatography mass spectrometry, using a deuterated analogue of the nucleoside as an internal standard and an antibody-mediated extraction procedure. Polyclonal antibodies were raised against the PhIP-nucleotide, PhIP-nucleoside and PhIP-guanine base adducts conjugated to keyhole limpet haemocyanin. Following their evaluation, the immobilized PhIP nucleotide antibody was used for the extraction of N(2)-(2'-deoxyguanosin-8-yl)PhIP from urine. The limit of detection of the assay was 125 pg and the limit of quantification 200 pg for a 50 ml human urine sample. Following oral administration of PhIP (20 mg/kg body wt/day) to rats for 6 days, N(2)-(2'-deoxyguanosin-8-yl) PhIP was readily detected in the urine, reaching steady state over 3 days. This is the first direct demonstration of the urinary elimination of this adduct following exposure to parent amine. The half-life of the adduct with DNA was estimated to be approximately 20 h. The total amount of PhIP recovered in the urine as adduct was <0.5 x 10(-3)% of the dose administered. Levels of the PhIP adduct in urine collections from human subjects ingesting the amine (4.9 micro g) in cooked meat were below the limits of detection, indicating that humans are exposed to a bioactive dose of <3 x 10(-4) of that associated with a non-carcinogenic level in rats.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1053-62
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Urinary N2-(2'-deoxyguanosin-8-yl)PhIP as a biomarker for PhIP exposure.
pubmed:affiliation
Section of Experimental Medicine and Toxicolog, Division of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 ONN, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't