The relationship of terminal duct hyperplasia to mammary carcinoma in 7,12-dimethylbenz(alpha)anthracene-treated LEW/Mai rats.
The evolution of dysplasias and carcinomas in the inguinal mammary glands of LEW/Mai rats given 7,12-dimethylbenz(alpha)anthracene (DMBA) by gastric gavage was studied with the use of stained whole mounts. Two major dysplasias, hyperplastic terminal end buds (HEBs) and hyperplastic alveolar nodules (HANs), developed prior to mammary carcinomas. HEBs were present in the mammary glands of approximately 70% of the rats within 1 week following DMBA. The percentage of rats with these lesions and the incidence of HEBs in the mammary gland decreased prior to the appearance of palpable and microscopic tumors. During the time when tumors first became evident (40-80 days), the percentage of rats with HEBs (11%) paralleled the percentage of rats with mammary tumors (12%). The initial percentage of rats with HEBs ( approximately 70%) paralleled the final tumor incidence (71%) observed in DMBA-treated rats that were allowed to live until they developed tumors. The histologic features of HEBs resembled those of the carcinomas, and HEBs were present in the immediate vicinity of some of the microscopic and palpable tumors. With only one exception, the location of microscopic tumors in the mammary gland was consistent with their derivation from small terminal ducts. These data are compatible with a developmental relationship between HEBs and mammary carcinoma. HANs, on the other hand, developed relatively late (ie, 30 days) following DMBA administration and became more numerous with the passage of time. Over the period of time when mammary carcinomas first became evident, the percentage of rats with HANs (73%) was inconsistent with a developmental relationship between HANs and mammary carcinoma. This conclusion was supported by the absence of HANs in the vicinity of microscopic tumors, by the dissimilarity between the histologic features of HANs and mammary carcinomas, and by their absence from the mammary gland during the time when at least some of the mammary tumors must have arisen. The results implicate terminal duct hyperplasia in the histopathogenesis of rat mammary carcinomas.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D005260:Female; D006965:Hyperplasia / Q000473:pathology; D008321:Mammary Glands, Animal / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D011917:Rats, Inbred Lew
D015127:9,10-Dimethyl-1,2-benzanthracene