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Adrenal Regulation of Mammary Tumorigenesis in Female Sprague-Dawley Rats: Histopathology of Mammary Tumors¹

Wood Hudson Cancer Research Laboratory, Covington, Kentucky 41011 [J. H. C., H. W. C.], and Department of Laboratory Medicine, St. Elizabeth Medical Center, Covington and Edgewood, Kentucky 41015 [H. W. C.]

Mammary tumors induced in female Sprague-Dawley rats by feeding 7,12-dimethylbenz(a)anthracene (DMBA; 20 mg/100 g body weight) were classified according to histological criteria of tissue differentiation, cellular atypia, and evidence of invasion. The 549 tumors could be placed in three categories, nodular hyperplasia, nodular hyperplasia with atypia, and carcinoma, and combinations of all three. Although tumors classified histologically as carcinomas did not metastasize, upon transplantation to the kidney capsule, a tumor classified as a carcinoma grew for eight generations and metastasized. Tumor heterogeneity was a common finding in DMBA-initiated tumors. Carcinomas were an early lesion. As the length of time between DMBA treatment and sacrifice increased, more tumors with areas of carcinoma were found. Therefore, DMBA-initiated tumors progressed to carcinomas either soon after initiation or later by development within nodular hyperplasias. In 4 separate groups of animals (74 adrenalectomized rats and 90 intact rats), postinitiation adrenalectomy increased the numbers of carcinomas compared to intact animals. This effect was consistently seen in the cervical and thoracic mammary glands. We propose that the mechanism for enhancement of progression to greater malignancy by adrenalectomy may be inhibition of differentiation of initiated cells in the absence of glucocorticoids.

¹ Major portions of this work were performed at the Cancer Research Institute of the New England Deaconess Hospital, Boston, MA, and were supported by the Atomic Energy Commission [Contracts AT (30-1)-3777 and AT (30-1)-3779].

² To whom requests for reprints should be addressed, at Wood Hudson Cancer Research Laboratory, 1830 Greenup Street, Covington, KY 41011.

Received 11/ 3/87. Revised 3/21/88. Accepted 4/ 6/88.

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