Endometrial adenomatous hyperplasia and carcinoma and multiple endocrinopathies in rats exposed to N-nitrosomethylurea.

Female Sprague-Dawley strain rats were given 3 i.v. injections of N-nitrosomethylurea, 4 mg/100 g body weight, at 4 weekly intervals. All rats developed mammary tumors, which were then excised to prolong survival. Seven months after the first injection, 14 of 27 (52%) rats examined has adenomatous hyperplasia of the endometrium, and 6 (22%) had endometrial carcinomas. The remaining 7 animals had varying degrees of hyperplasia, some with squamous metaplasia. Endocrine pathology in these same rats included hyperplasia of the eosinophilic and basophilic cells of the hypophysis (100%), adrenocortical adenomas (81%), polycystic ovaries (70%), thyroid follicular enlargement with colloid accumulation (67%), and parathyroid hyperplasia (7%). Serum TSH levels were elevated in the rats with thyroid abnormalities.