DNA Synthesis in Pre-Cancerous Nodules of the Mouse Mammary Gland

Authors

Richard D. Adamson, University of Nebraska-Lincoln

Document Type

Thesis

Date of this Version

7-1970

Citation

Thesis (M.S.)—University of Nebraska—Lincoln, 1970. Department of Zoology.

Comments

Copyright 1970, the author. Used by permission.

Abstract

DNA synthesis and growth profile were determined in MTV-free hormone-induced D₁ hyperplastic alveolar mammary gland nodule of BALB/c mouse at weekly intervals following fat-pad transplantation. Methods used were autoradiography, liquid scintillation counting, and histology. The number of alveolar cells entering DNA synthesis determined by autoradiography in hormone-induced D₁ outgrowths reached a peak two weeks after transplantation and this is followed by a plateau and finally a decline. Also, during the second week, alveolar cells are synthesizing DNA at a faster rate, as evidenced by an increase in the average number of silver grains per nucleus in D₁ HAN. DNA synthesis (measured by radiochemical method) of the fat-pad containing the outgrowth reached a peak during the fourth week and this was followed by a plateau and finally a decline. The outgrowth does not grow exponentially, and there are periods of rapid proliferation followed by periods of less active growth. It has been suggested that there may be a relationship between rate of DNA synthesis in D₁ HAN after transplantation and optimal time of application of the carcinogen 3-methylcholanthrene leading to tumor induction.

The effect of ovariectomy on two outgrowth lines of MTV-free, hormone induced D₂ and D₇ hyperplastic alveolar nodules (HAN) of BALB/c mouse mammary gland was determined by ³H-thymidine autoradiography. DNA synthesis in the cells of normal mammary glands collected from virgin hosts decreased significantly after bilateral ovariectomy. Frequency of alveolar cells labeled with ³H-TdR in the low tumor-producing D₇ series dropped significantly following the ovaries in a manner similar to that of normal mammary tissue. DNA synthesis in the high tumor-producing D₂ series continued in the absence of the ovaries as evidenced by the high values for frequency of ³H-TdR labeled nuclei five days following the operation. It is suggested that alveolar cells of the D₂ outgrowth line have an altered response to host hormonal control on DNA synthesis. A possible relationship between tumor-producing capabilities and alterations in host hormonal control on DNA synthesis in BALB/c HAN tissues has been discussed.

Advisor: Mihir R. Banerjee