Lack of Modification by Environmental Estrogenic Compounds of Thyroid Carcinogenesis in Ovariectomized Rats Pretreated with N ‐bis(2‐hydroxypropyl)nitrosamine (DHPN)

The effects of environmental estrogenic compounds, soy isoflavone mixture (SI), genistein (GEN), and nonylphenol (NP), and the possible goitrogen 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5 H )‐furanone (MX), on thyroid carcinogenesis were investigated in ovariectomized (OVX) female rats. Five‐week‐old OVX F344 rats were given a single subcutaneous injection of N ‐bis(2‐hydroxypropyl) nitrosamine (DHPN; 2400 mg/kg, body weight) or vehicle alone. Starting 1 week later, GEN (250 or 25 ppm in diet), SI (400 ppm in diet), NP (250 or 25 ppm in diet), MX (30 ppm, in drinking water), sulfadimethoxine (SDM), a known thyroid tumor‐promoter (1000 ppm in drinking water), or β‐estradiol 3‐benzoate (EB), a synthetic estrogen (0.5 mg in cholesterol pellet, s.c.) were administered for 12 weeks. SDM and EB were included as positive controls. At sacrifice the major organs including the thyroid, pituitary, liver, kidney, uterus, vagina, brain and pancreas were collected and histopathological observation was performed. Thyroid weights were significantly increased ( P < 0.001) only in the SDM treatment group and pituitary weights were elevated with SDM ( P < 0.05) and EB ( P < 0.001). Kidney and uterus weights were also significantly increased ( P < 0.05) by EB. Histopathologically, proliferative lesions of the thyroid were only observed in the SDM treatment group and of the pituitary in the SDM or EB treatment groups. Renal tubule lesions, uterine squamous metaplasia, vaginal keratinization and telangiectasia of pancreatic islets were also observed with EB. There were no organ weight changes or histopathological lesions in the major organs, including the thyroid, in the GEN, SI, MX or NP treatment groups. Our results thus indicated a lack of modifying effects on thyroid carcinogenesis in female OVX rats, in agreement with our previous finding in males.