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Rate of Nucleic Acid Synthesis in Mammary Hyperplastic Alveolar Nodule Outgrowths and Transplanted Adenocarcinomas in Pregnant and Lactating Mice¹

Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center of Northern California, Oakland, California 94609

The in vitro synthesis of RNA and DNA was measured in normal tissues and in serially transplanted outgrowths of hyperplastic alveolar nodules and adenocarcinomas of mammary glands of pregnant and lactating C3H/Crl mice. The rate of DNA synthesis (incorporation of thymidine) in normal glands of mice at midlactation was only 12% of that in glands from mice in late pregnancy. A decrease of 40% in the rate of RNA synthesis (incorporation of uridine) was observed in the glands during transition from late pregnancy to midlactation.

The rate of synthesis of RNA in the preneoplastic hyperplastic alveolar nodule was unaffected by the transition of the host from the nulliparous to the pregnant state but was significantly decreased by the onset of lactation. On the other hand, the rate of DNA synthesis in the hyperplastic alveolar nodule was not significantly altered by these changes in the physiological state of the host. In contrast to that in the preneoplastic gland, RNA synthesis in the neoplastic tissue was not significantly altered by changes in the physiological state of the host, but the rates of DNA synthesis in tumors from nulliparous mice were significantly lower than those in adenocarcinomas from lactating mice. To test whether the responses of the preneoplastic and neoplastic tissues were related to the hormonal changes in the host, we examined nucleic acid synthesis in these tissues taken from mice that had been hypophysectomized 5 to 7 days earlier. Although the rate of RNA synthesis was unchanged in the tissues from the hypophysectomized mice, the rate of DNA synthesis was only 30% of that in comparable tissues from intact mice.

The results of these studies are consistent with the concept that the preneoplastic and neoplastic mammary tissues of mice are sensitive to hormones. Evidently, the levels circulating in the quiescent state are sufficient to maintain nucleic acid synthesis so that changes due to pregnancy and lactation have no effect. When pituitary hormones are withdrawn by hypophysectomy, the dramatic decrease in the rate of DNA synthesis reveals the hormonal dependence of these abnormal mammary tissues.

¹ This is Paper 4 of the series, "Metabolic Characteristics of a Naturally Occurring Preneoplastic Tissue." This research was supported by USPHS Research Grant CA-11736 from the National Cancer Institute.

Received 3/19/74. Accepted 6/26/74.