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Carcinogenesis Advance Access published online on May 16, 2006
Carcinogenesis, doi:10.1093/carcin/bgl072
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received November 28, 2005
Revised April 25, 2006
Accepted May 5, 2006

CARCINOGENESIS

Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon, dibenzo[a,l]pyrene

Zhen Yu 1, Brinda Mahadevan 2, Christiane V. Löhr 3, Kay A. Fischer 3, Mandy A. Louderback 2, Sharon K. Krueger 1, Clifford B. Pereira 4, Daniel J. Albershardt 2, William M. Baird 5, George S. Bailey 6, and David E. Williams 6 *

1 Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR; The Linus Pauling Institute, Oregon State University, Corvallis, OR
2 Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR
3 College of Veterinary Medicine, Oregon State University, Corvallis, OR; Environmental Health Sciences Center, Oregon State University, Corvallis, OR
4 Environmental Health Sciences Center, Oregon State University, Corvallis, OR; Department of Statistics, Oregon State University, Corvallis, OR
5 Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR; Environmental Health Sciences Center, Oregon State University, Corvallis, OR
6 Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR; The Linus Pauling Institute, Oregon State University, Corvallis, OR; Environmental Health Sciences Center, Oregon State University, Corvallis, OR

* To whom correspondence should be addressed.
David E. Williams, E-mail: david.williams{at}oregonstate.edu


  Abstract

The fetus and neonate are sensitive targets for chemically induced carcinogenesis. Few studies have examined the risk/benefit of chemoprotective phytochemicals, given in the maternal diet, against transplacental carcinogenesis. In this study, B6129 SF1/J (AHRb-1/d) and 129Sv/ImJ (AHRd/d) mice were cross bred. The polycyclic aromatic hydrocarbon, dibenzo[a,l]pyrene (DBP), was administered to pregnant mice (15 mg/Kg, gavage) on gestation day 17 and 2000 ppm indole-3- carbinol (I3C), a chemoprotective phytochemical from cruciferous vegetables, was fed to half of the mice from gestation day 9 until weaning. Offspring born to dams fed I3C exhibited markedly fewer mortalities (p<0.0001). Maternal dietary exposure to I3C also significantly lowered lung tumor multiplicity (p = 0.035) in offspring surviving to 10 months of age. The I3C chemoprotection was independent of either maternal or fetal AHR genotype. The bioavailability of DBP to fetal target tissue was demonstrated by assessing DNA covalent adduction with a 33P-post-labeling assay. The bioavailability of I3C was determined by dosing a subset of pregnant mice with [14C]-I3C. Addition of chemoprotective agents to the maternal diet during pregnancy and nursing may be an effective new approach in reducing the incidence of cancers in children and young adults.


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