Linked Life Data

12030841

Source:http://linkedlifedata.com/resource/pubmed/id/12030841

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-5-28
pubmed:abstractText
Dose responses of the characteristic short-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HxCDD), and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) were compared in the resistant Han/Wistar (Kuopio) (H/W) rats and the sensitive Long-Evans (Turku/AB) (L-E) rats. The resistance of H/W rats is linked to the altered H/W-type aryl hydrocarbon receptor (AHR). Exceptionally, in terms of acute lethality, the most potent congener for H/W rats is HxCDD, followed by HpCDD, PeCDD, and TCDD. The study objectives were to find out if this exceptional sensitivity of H/W rats also holds for nonlethal toxic endpoints and to compare potency and efficacy (magnitude of effect) of PCDDs between L-E and H/W rats. Dose responses for several endpoints were determined, modeled, and used for ED50 and relative potency (REP) calculations. For all endpoints measured, TCDD was the most potent congener, followed by PeCDD, HxCDD, and HpCDD in both strains, and the REP estimates were consistent with the current toxic equivalency factors (TEFs). For most endpoints, H/W rats showed smaller responses to all congeners than L-E rats, and this difference was due to lower efficacy rather than lower potency. H/W rats showed lower efficacy to body weight loss, serum aspartate aminotransferase activity, and serum concentrations of total bilirubin, free fatty acids, and thyroxine. In contrast, effects on cytochrome P4501A1 induction, thymus atrophy, and dental defects were similar in both strains. In conclusion, the results are in agreement with the current WHO-TEFs and imply that relative potency values derived from mortality are not necessarily valid for other endpoints. The results support our previous observations about two different types of AHR-mediated mechanisms. Type I effects are similar in both strains, and type II effects show decreased efficacy of toxic response in relation with the altered H/W-type AHR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
(c) 2002 Elsevier Science (USA).
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
181
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38-47
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12030841-Animals, pubmed-meshheading:12030841-Body Weight, pubmed-meshheading:12030841-Cytochrome P-450 CYP1A1, pubmed-meshheading:12030841-Dose-Response Relationship, Drug, pubmed-meshheading:12030841-Drug Resistance, pubmed-meshheading:12030841-Female, pubmed-meshheading:12030841-Genetic Predisposition to Disease, pubmed-meshheading:12030841-Lethal Dose 50, pubmed-meshheading:12030841-Liver, pubmed-meshheading:12030841-Organ Size, pubmed-meshheading:12030841-Rats, pubmed-meshheading:12030841-Rats, Long-Evans, pubmed-meshheading:12030841-Rats, Wistar, pubmed-meshheading:12030841-Species Specificity, pubmed-meshheading:12030841-Specific Pathogen-Free Organisms, pubmed-meshheading:12030841-Structure-Activity Relationship, pubmed-meshheading:12030841-Tetrachlorodibenzodioxin, pubmed-meshheading:12030841-Thymus Gland
pubmed:year
2002
pubmed:articleTitle
Structure-activity relationships and dose responses of polychlorinated dibenzo-p-dioxins for short-term effects in 2,3,7,8-tetrachlorodibenzo-p-dioxin-resistant and -sensitive rat strains.
pubmed:affiliation
Department of Environmental Health, National Public Health Institute, Kuopio, Finland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't