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ToxSci Advance Access published online on July 26, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm179
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Published by Oxford University Press 2007.

Relationships Between Tissue Levels of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), mRNAs and Toxicity in the Developing Male Wistar(Han) Rat

David R. Bell*,lll, Sally Clode{dagger}, Ming Qi Fan*, Alwyn Fernandes, Paul M.D. Foster{ddagger}, Tao Jiang*, George Loizou§, Alan MacNicoll, Brian G. Miller||, Martin Rose, Lang Tran|| and Shaun White

* School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK {dagger} Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire, HG3 1PY, UK {ddagger} NIEHS, PO Box 12233 (MD E1-06), 111 TW Alexander Drive, Research Triangle Park, NC 27709 USA § Health & Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 9JN, UK Central Science Laboratory, Environment, Food and Health, Sand Hutton, York YO41 1LZ, UK || Institute of Occupational Medicine, Research Park North, Riccarton, Edinburgh, EH14 4AP, UK

lll To whom correspondence should be addressed. E-mail: david.bell{at}nottingham.ac.uk Fax: (44) 115 9513251

Received May 23, 2007; revision received June 29, 2007; accepted July 5, 2007


  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.

Key Words: Dioxin; Sperm; developmental; toxicity; balanopreputial separation; puberty.


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T. Jiang, D. R. Bell, S. Clode, M. Q. Fan, A. Fernandes, P. M. D. Foster, G. Loizou, A. MacNicoll, B. G. Miller, M. Rose, et al.
A Truncation in the Aryl Hydrocarbon Receptor of the CRL:WI(Han) Rat Does Not Affect the Developmental Toxicity of TCDD
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[Abstract] [Full Text] [PDF]


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