The effect of perphenazine, a phenothiazine derivative, on serum prolactin levels, on maturation of the normal mammae, and on growth of mammary adenocarcinomas was studied using two transplantable rat mammary tumor systems, the 13762 mammary tumor (13762 MT) in the syngeneic Fischer 344 strain and the R-35 mammary tumor (R-35 MT) in allogeneic Sprague-Dawley stock. Perphenazine induced a dose-response increase in the serum prolactin levels of both normal and tumor-bearing animals and stimulated maturation of the normal mammae. The resultant responses of the two mammary tumors to perphenazine treatment were in exact contrast. Growth of the 13762 MT was accelerated whereas growth of the R-35 MT was inhibited. There was atrophy of the mammae and a concomitant decrease in serum prolactin levels in young, sexually maturing females with progressively growing 13762 MT tumors. Normal mammae and serum prolactin levels were unaffected in similar females bearing the R-35 MT. Treatment of the hosts with estrogen prior to tumor implantation, as well as treatment of both tumor and host, enhanced the effects of perphenazine on serum prolactin levels, on the normal mammae, and on mammary tumor growth, i.e., stimulation of 13762 MT and inhibition of R-35 MT.


This investigation was supported by Contract PH43-65-6 from the Endocrine Evaluation Branch, General Laboratories and Clinics, National Cancer Institute, NIH.

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