Female C3H/HeN-MTV—mice were fed DES (0, 10, 40, 160, 640, or 1280 ppb) continuously. They were palpated weekly for mammary tumors and killed when masses reached a 1 cm diameter or at scheduled periods of 6, 12, 18, 24, or 30 months of exposure. Dead and moribund mice were examined histologically. In scheduled-sacrifice animals, mammary tumors were more prevalent than in controls at 640 and 1280 ppb. Time-to-removal with palpable tumors was reduced at and above 40 ppb. Pituitary adenomas, endometrial and cervical adenocarcinomas, and peritoneal mesotheliomas were more frequent and occurred earlier than in controls at 160 ppb or above. In scheduled-sacrifice animals fed 40 ppb, prevalences of several nonneoplastic findings were increased, including uterine grandular hyperplasia, cervical adenosis, splenic hypererythropoiesis, osseous trabecular proliferation, and mammary hyperplastic alveolar nodules. Corpora luteal depletion, pituitary cystoid degeneration, and sternal osteofibrosis were more prevalent at or above 160 ppb than in controls. Among mice removed at unscheduled periods, mammary tumors and nonneoplastic changes tended to be more frequent than in controls, even at 10 ppb DES. This study shows that exposure of mice to DES levels causing nonneoplastic alterations is also likely to increase neoplastic effects with time and suggests that any efficacious use of DES as a human drug increases the probability of cancer to an extent related to the drug-induced increase in estrogenic body burden.
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