ToxSci Advance Access originally published online on July 26, 2007
Toxicological Sciences 2007 99(2):591-604; doi:10.1093/toxsci/kfm179
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
* School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom
Covance Laboratories, Ltd., Harrogate, North Yorkshire HG3 1PY, United Kingdom
NIEHS, Research Triangle Park, North Carolina 27709
Health & Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 9JN, United Kingdom
¶ Central Science Laboratory, Environment, Food and Health, Sand Hutton, York YO41 1LZ, United Kingdom
|| Institute of Occupational Medicine, Research Park North, Riccarton, Edinburgh EH14 4AP, United Kingdom
1 To whom correspondence should be addressed. Fax: +44 115 9513251. E-mail: david.bell{at}nottingham.ac.uk.
Received May 23, 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 gestation day (GD)16 and GD21, and from offspring on postnatal days (PND)70 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 (BPS), and the greater induction of CYP1A1 RNA in PND70 offspring liver from chronically-dosed dams suggests that lactational transfer of TCDD is crucial to this toxicity. These data characterize 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 BPS between the two studies.
Key Words: dioxin; sperm; developmental; toxicity; balanopreputial separation; puberty.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Simon, L. L. Aylward, C. R. Kirman, J. C. Rowlands, and R. A. Budinsky Estimates of Cancer Potency of 2,3,7,8-Tetrachlorodibenzo(p)dioxin Using Linear and Nonlinear Dose-Response Modeling and Toxicokinetics Toxicol. Sci., December 1, 2009; 112(2): 490 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 Toxicol. Sci., February 1, 2009; 107(2): 512 - 521. [Abstract] [Full Text] [PDF]
|
|