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Relationships between tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mRNAs and toxicity in the developing male Wistar(Han) rat

Bell, David Robert; Clode, Sally; Fan, MingQi; Fernandes, Alwyn; Foster, Paul M D; Jiang, tao; Loizou, George; MacNicoll, Alan; Miller, Brian G; Rose, Martin; Tran, Lang; White, Shaun

Authors

David Robert Bell david.bell@nottingham.ac.uk

Sally Clode

MingQi Fan

Alwyn Fernandes

Paul M D Foster

tao Jiang

George Loizou

Alan MacNicoll

Brian G Miller

Martin Rose

Lang Tran

Shaun White



Abstract

We compared the effects of a single acute dose, or chronic fetal exposure, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the male reproductive system of the Wistar(Han) rat. Tissue samples were taken from dams on GD16 and GD21, and from offspring on PND70 and 120. Steady state concentration of TCDD was demonstrated in the chronic study: body burdens were comparable in both studies. Fetal TCDD concentrations were comparable after acute and chronic exposure, and demonstrate more potent toxicity after chronic versus acute dosing. In maternal liver, cytochrome P450 (CYP)1A1 and CYP1A2 RNA were induced. In fetus, there was induction of both CYP1A1 and CYP1A2 RNA at medium and high doses, but inadequate evidence for induction at low dose in either study. The low level induction of CYP1A1 RNA at low dose in fetus argues against AhR activation in fetus as a mechanism of toxicity of TCDD in causing delay in balanopreputial separation, and the greater induction of CYP1A1 RNA in PND70 offspring liver suggests that lactational transfer of TCDD is crucial to this toxicity. These data characterise the maternal and fetal disposition of TCDD, induction of CYP1A1 RNA as a measure of AhR activation, and suggest that lactational transfer of TCDD determines the difference in delay in balanopreputial separation between the two studies.

Journal Article Type Article
Publication Date Oct 1, 2007
Journal Toxicological Sciences
Print ISSN 1096-6080
Electronic ISSN 1096-6080
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 99
Issue 2
APA6 Citation Bell, D. R., Clode, S., Fan, M., Fernandes, A., Foster, P. M. D., Jiang, T., …White, S. (2007). Relationships between tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mRNAs and toxicity in the developing male Wistar(Han) rat. Toxicological Sciences, 99(2),
Keywords 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mRNAs, toxicity, Wistar(Han) rat
Publisher URL http://toxsci.oxfordjournals.org/cgi/content/abstract/kfm179?ijkey=w4SKS12ayGBWqI1&keytype=ref
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Toxicological Sciences following peer review. The definitive publisher-authenticated version Bell, David Robert and Clode, Sally and Fan, MingQi and Fernandes, Alwyn and Foster, Paul M D and Jiang, tao and Loizou, George and MacNicoll, Alan and Miller, Brian G and Rose, Martin and Tran, Lang and White, Shaun (2007) Relationships between tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mRNAs and toxicity in the developing male Wistar(Han) rat. Toxicological Sciences, 99 (2). pp. 591-604. is available online at:[http://toxsci.oxfordjou...2ayGBWqI1&keytype=ref].

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TCDD_and_RNA_full.pdf (11 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


SupplementaryFull.pdf (7.1 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


AllTCDDandRNAdata.xls (99 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf



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