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Vet Pathol 46:142-150 (2009)
© 2009 American College of Veterinary Pathologists


ENVIRONMENTAL PATHOBIOLOGY

Effects of Neonatally Administered High-dose Diethylstilbestrol on the Induction of Mammary Tumors Induced by 7,12-Dimethylbenz[a]anthracene in Female Rats

H. Kawaguchi, Y. Umekita, M. Souda, K. Gejima, H. Kawashima, T. Yoshikawa and H. Yoshida

Departments of Tumor Pathology, Field of Oncology (HK, YU, MS, HY); and Thoracic and Cardiovascular Surgery, Hepato-Biliary-Pancreatic Surgery (KG, HK); Kagoshima University Graduate School of Medical and Dental Sciences, and Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan (TY)

Abstract

The aim of this study was to investigate the effects of neonatal administration of a relatively high dose of diethylstilbestrol (DES) on the induction of mammary carcinomas (MCs) and benign proliferative lesions (PLs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Three different terms of daily administration of DES (10 µg) were used: 0–14, 0–5, and 6–14 days after birth. Control animals were administered solvent (oil) alone once daily from 0 to 14 days after birth. Rats were given DMBA (10 mg) at 50 days after birth. All rats administered DES showed persistent estrus and anovulatory ovaries. In rats administered DES from 0 to 14 and 0 to 5 days after birth there was protection from development of MCs and PLs, and serum levels of both estrogen and progesterone were significantly lower than in the control animals at 100 days after birth. In rats administered DES from 6 to 14 days after birth, the incidence of MCs was equal to that of the control animals (100%), and the number of PLs was significantly higher than in the control animals. The critical period for exposure to endocrine disruptors, such as DES, affecting the induction of MCs and PLs may be from 0 to 5 days after birth.


Key words: Diethylstilbestrol (DES); endocrine disruptor; mammary tumor; neonatal period; rat; 7,12-dimethylbenz[a]anthracene (DMBA).

Request reprints from Dr. H Kawaguchi, Department of Tumor Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan). E-mail: kawa{at}m3.kufm.kagoshima-u.ac.jp


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