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

Authors

Richard D. Adamson, University of Nebraska-Lincoln

Date of this Version

7-1970

Document Type

Thesis

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