Serial Transplantation of Chemical Carcinogen-Induced Mouse Mammary Ductal Dysplasias2

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Abstract
ALB/c and (C57BL × DBAf)F, mice were treated with 7,12-dimethylbenz[a]anthracene and urethan, respectively, to induce mammary dysplasias. Nine transplantable outgrowth lines of dysplastic tissue were established by transplantation of the primary lesions into the cleared mammary fat pads of syngeneic mice; 8 of the 9 lesions were ductal in origin. The growth and tumorigenic potentials of these 9 lines were followed over 6-9 transplant generations. Most outgrowth lines exhibited a rapid decline in growth potential and/or a progression to papillomatosis and subsequent carcinoma by transplant generation 7. The ductal outgrowth lines and mammary tumors established from urethan-induced dysplasias in hybrid mice were ovarydependent for tumorigenesis and tumor growth. The transplantation experiments confirmed the hypothesis that ductal dysplasias have high tumorigenic potentials and can be classified as “highrisk” lesions, similar to murine mammary tumor virus-induced hyperplastic alveolar nodules.