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Comparison of the Effects of Hormones on DNA Synthesis in Cell Cultures of Nonneoplastic and Neoplastic Mammary Epithelium from Rats

Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London, WC2A 3PX, England [R. C. H., P. S. R., D. J. L., D. B., H. D.], and Department of Clinical Surgery, University Medical School, Edinburgh, EH8 9AG, Scotland [R. A. H.]

Mammary glands from virgin and perphenazine [1,2-hydroxyethyl-4,3-(2-chloro-10-phenothiazinyl)piperazine]-treated rats, hormone-dependent mammary tumors induced by dimethylbenzanthracene, and hormone-independent transplantable mammary tumors were digested with enzymes. Cells from the resulting epithelial microexplants and stroma were grown on plastic dishes in Medium 199 with fetal calf serum either with or without mammotrophic hormones. To determine the effects of mammotrophic hormones on the growth of the cultured cells, tritiated thymidine was added during the growth phase and its uptake into DNA was measured.

[³H]DNA synthesis of the stromal cells was not altered by the addition of mammotrophic hormones. [³H]DNA synthesis of the epithelial cultures from the transplantable tumors was insensitive to mammotrophic hormones, whereas that from nonneoplastic mammary glands and from induced tumors was stimulated by the addition of prolactin, glucocorticoids, insulin, and progesterone. Epithelial cultures from virgin and perphenazine-treated rats required both corticosterone and insulin for prolactin to initiate significant increases in [³H]DNA synthesis, whereas prolactin alone stimulated [³H]DNA synthesis in epithelial cultures from dimethylbenzanthracene-induced tumors. The effects of hormones on DNA synthesis in cell cultures from the different mammary tissues were similar to the influence of these hormones on the growth of mammary tissues in vivo.

Received 9/17/76. Accepted 5/ 6/77.