Occurrence and Transplantation of Carcinogen-Induced Hyperplastic Nodules in Fischer Rats

Female inbred Fischer rats, age 50–60 days, were given 10, 15, or 20 mg 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil in a single dose by gastric intubation. Mammary gland tumors or hyperplastic nodules, or both, were found in all treated animals, whereas none was observed in the sesame oil-treated controls. Nodules appeared with about equal frequency in all dose groups. However, the number of lesions in all groups increased with time after carcinogen administration. Similar lesions were seen in the mammary glands of old male and multiparous female rats. The hyperplastic structures observed in the mammary glands of DMBA-treated female rats were placed into four categories by morphologic criteria derived from stained wholemounts and histologic sections: hyperplastic alveolar nodules, distended alveolar nodules, fibrous nodules, and ductal hyperplasias. Eighty hyperplastic alveolar nodules were seen in the mammary glands of anesthetized animals by intraductal injection of the animal's blood. These nodules were transplanted into the abdominal gland-free mammary fat pads of 3-week-old female rats. No tumors developed in the hyperplastic outgrowths of the transplanted nodules. Outgrowths showed a variety of patterns. OF the carcinogen-treated normal tissues placed in the contralateral fat pads, none produced hyperplastic outgrowths as such, although 9% showed hyperplastic nodules in the otherwise normal outgrowths. It is apparent that both a variety of hyperplastic lesions and tumors result from the action of DMBA on rat mammary glands. Although the hyperplastic alveolar lesions give rise to hyperplastic outgrowths on transplantation, no tumors have yet been observed from such transplants within the test period. Thus these lesions in the rat must not yet be defined as preneoplastic.