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Toxicologic Pathology, Vol. 35, No. 6, 811-816 (2007)
DOI: 10.1080/01926230701584205
© 2007 Society of Toxicologic Pathology

Articles

Effects of Neonatally Administered Diethylstilbestrol on Induction of Mammary Carcinomas Induced by 7, 12-Dimethylbenz[A]Anthracene in Female Rats

Kenjiro Ninomiya1, Hiroaki Kawaguchi1, Masakazu Souda1, Shuuhei Taguchi1, Mamoru Funato1,2, Yoshihisa Umekita1 and Hiroki Yoshida1

1 Department of Tumor Pathology, Field of Oncology, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544 Japan
2 Drug Safety Research Laboratories, Shin Nippon Biochemical Laboratories, Ltd., Kagoshima 891-1394 Japan

Correspondence: Address Hiroaki Kawaguchi, D.V.M., Ph. D., 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

Various doses of diethylstilbestrol (DES) were administered to rats once at birth. Thereafter, at 50 days after birth, the rats in all groups were given 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) and undergone necropsy at 300 days after birth. The incidence of mammary carcinomas (MCs) were 50, 54, 91, 39, 19% at 175 days after birth, and 77, 87, 100, 85, 75% at necropsy in the 0, 0.1, 1, 10, 100 µg groups, respectively. The incidence of rats without corpus luteum were 0, 0, 0, 30, 100% at 50 days after birth, and 0, 40, 53, 93, 100% at necropsy in the 0, 0.1, 1, 10, 100 µg groups, respectively. Observation of the whole mount specimens showed a higher number of terminal end buds (TEBs) in the 1 µg group and a lower number in the 100 µg group compared with the control at 50 days after birth. It suggested that the administration of a relatively low dose (1 µg) of DES during neonatal period may increase TEBs, thus resulting in a stimulatory effect on the initiation of MCs.

Key Words: Mammary carcinoma • diethylstilbestrol (DES) • 7, 12-dimethylbenz[a]anthracene (DMBA) • endocrine disruptors • neonatal • terminal end bud • rat pathology

Abbreviations: DES, diethylstilbestrol • DMBA 7, 12-dimethylbenz [a]anthracene • MCs, mammary carcinomas • TEBs, terminal end buds • PE, persistent estrus • SD, Sprague-Dawley • H.E., hematoxylin and eosin • CL, corpus luteum • DAB, 3,3'-diaminobenzidine tetrachloride • SD, standard deviation • BW, body weight • AW, absolute weight • E2, 17β-estradiol • TP, testosterone propionate • ABs, alveolar buds • LOBs, lobules


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