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ToxSci Advance Access published online on September 26, 2003

Toxicological Sciences, doi:10.1093/toxsci/kfg247
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received June 27, 2003; accepted September 11, 2003
© 2003 Society of Toxicology

Reproductive and Developmental Toxicology

Mammary Gland Morphology in Sprague Dawley Rats Following Treatment with an Organochlorine Mixture in Utero and Neonatal Genistein

Warren G. Foster 1*, Edward V. Younglai 1, Odette Boutross-Tadross 2, Claude L. Hughes 3, and Michael G. Wade 4

1 Department of Obstetrics and Gynecology, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada
2 Department of Pathology and Molecular Medicine, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada
3 Department of Obstetrics & Gynecology, Duke University Medical Center, Durham, NC, USA
4 Systemic Toxicology and Pharmacokinetics Section, Environmental and Occupational Toxicology Division, Environmental Health Science Bureau, Health Canada; Environmental Health Centre, Tunney's Pasture, Ottawa, Ontario, Canada

* To whom correspondence should be addressed. E-mail: fosterw{at}mcmaster.ca.


   Abstract

In a related reproductive toxicology study designed to investigate the effects of in utero exposure to environmental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology. Time mated Sprague Dawley rats were treated on days 9-16 of gestation with vehicle or a mixture of environmental toxicants at 1 X the acceptable daily intake. Furthermore, it is unclear whether postnatal exposure to phytoestrogens in soy-formulas poses breast cancer benefit or risk and potential interactions with environmental toxicants are unknown. Therefore, half the female pups from each treatment group either received subcutaneous vehicle or genistein (10 µg/g BW/day) on postnatal days 2-8. Following necropsy at 200 days of age, a pathologist blinded to treatment groups examined mammary gland histopathology. Only mild histological changes were found in mammary glands of rats exposed to the mixture in utero whilst pronounced ductal hyperplasia, lactational changes and fibrosis were observed in mammary glands from the genistein group and were more prominent in the mixture + genistein group. Mammary glands of the control group were histologically normal. Collectively our results reveal that postnatal exposure to pharmacological levels of genistein induces profound morphological changes in the mammary glands of adult female rats and that high levels of phytoestrogens possess the potential to modulate the toxicological effects of toxicant mixtures.

Key Words: Mixtures, genistein, mammary, tumors, and development .


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