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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-6-6
pubmed:abstractText
In this study, we investigated the time course of promotion of tumors and putatively preneoplastic altered hepatic foci in the livers of diethylnitrosamine (DEN)-initiated female Sprague-Dawley rats. These rats had been treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) under different dosing regimens, but we used the same administered biweekly dose of 1.75 microg/kg of body weight. Animals were treated continuously for up to 60 weeks, or continuously for 30 weeks, followed by cessation of treatment for up to 30 weeks. In addition, TCDD treatment in these groups was begun either 2 or 18 weeks after initiation with DEN. Liver tumors were only observed in animals after 60 weeks on the study and were increased by continuous TCDD treatment, relative to controls. The incidence of hepatocellular adenoma and carcinoma combined, in animals treated with TCDD for 30 weeks followed by no TCDD treatment for 30 weeks (17%), was lower than in animals receiving either TCDD (79%) or vehicle control (corn oil) alone (55%) for 60 weeks. The lower liver-tumor incidence after cessation of TCDD treatment paralleled time-dependent decreases in the volume fraction occupied by placental glutathione S-transferase-positive altered hepatic foci and the number of foci per unit volume, but not the mean focus volume that exhibited a time-dependent increase after cessation of TCDD treatment. Cessation of TCDD treatment led to reductions in liver TCDD levels, and these changes were reflected in a cessation of reduced body weight because of TCDD treatment. These data indicate that liver-tumor promotion by TCDD in female rats is dependent upon continuous exposure to TCDD, and that alterations in patterns of TCDD exposure can have significant effects on tumor incidence not reflected by standard measures of dioxin exposure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
330-7
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Hepatocarcinogenesis in female Sprague-Dawley rats following discontinuous treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
pubmed:affiliation
Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. walker3@niehs.nih.gov
pubmed:publicationType
Journal Article