Linked Life Data

8844800

Source:http://linkedlifedata.com/resource/pubmed/id/8844800

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-1-6
pubmed:abstractText
Estimating the cancer risk posed by heterocyclic amines depends on measuring how chemical dose influences measurable indicators of cancer progression. This data ideally should encompass the range of actual human exposure, at the low dose end, and laboratory animal studies, at the high dose end. Accelerator mass spectrometry (AMS) has been used to measure the absorption, fate, and DNA adduct dosimetry of the heterocyclic amines PhIP and MeIQx at doses equivalent to human consumption following single-dose administration and chronic daily dosing. AMS is a nuclear physics technique which specifically counts nuclei of cosmogenic isotopes, rather than relying on decay. For tracing 14C, sensitivity is increased 10(6)-fold relative to decay counting. We have found that tissue clearance rates for [2-(14)C]-PhIP are rapid (t1/2 = 1 h) at low dose (41 ng/kg), with most of the radiocarbon distributed to the liver and G.I. tract. MeIQx-DNA adduct levels decrease linearly with dose (5 mg/kg-500 ng/kg) in single dose exposures. Likewise, the biologically available dose of [2-(14)C]-MeIQx decreases linearly with decreasing dose (5 mg/kg-1 ng/kg). On chronic daily dosing, it takes 40 days for adducts to reach steady-state in tissues and adduct levels appear to decrease linearly with decreasing dose, except possibly at very low doses. DNA binding of PhIP involves both sulfation or acetylation of the N-hydroxylated PhIP. Quantitatively, sulfation appears to be an important pathway for PhIp activation in rodent tissue cytosols while acetylation appears quantitatively more important in human tissue cytosols. The greatest activity is in liver and intestinal tissues for both pathways. The specific DNA adducts formed in vivo and in vitro from exposure to PhIP and MeIQx are likely guanine adducts. These data suggest that DNA adduct dosimetry responds linearly with dose but may become sub-linear at very low doses for chronic exposure and that factors other than DNA adduction may be critical to explain these heterocyclic amines' tumorigenicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-102
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Assessment of the DNA adduction and pharmacokinetics of PhIP and MeIOx in rodents at doses approximating human exposure using the technique of accelerator mass spectrometry (AMS) and 32P-postlabeling.
pubmed:affiliation
Biomedical and Biotechnology Research Program/Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Review