ToxSci Advance Access originally published online on September 26, 2003
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Toxicological Sciences 77, 91-100 (2004)
Copyright © 2004 by the 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
* Departments of Obstetrics and Gynecology and
Pathology and Molecular Medicine, McMaster University and Health Sciences Centre, Hamilton, Ontario, Canada;
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina; and
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
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 1x 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 received either subcutaneous vehicle or genistein (10 µg/g body weight [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 while 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; development.
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