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Restriction Endonuclease Studies of Hyperplastic Outgrowth Lines from BALB/cfC3H Mouse Hyperplastic Mammary Nodules¹

Department of Pathology, School of Medicine [R. D. C., T. G. F., D. W. M., R. L. A.], and Department of Anatomy, School of Veterinary Medicine [L. J. F.], University of California, Davis, California 95616

The DNA's isolated from five mouse hyperplastic mammary gland outgrowth lines from BALB/cfC3H mice were digested with the restriction endonucleases PstI, BamHI, or EcoRI; electrophoresed; and analyzed by Southern blotting and autoradiography. Proviral DNA sequences from the acquired C3H mouse mammary tumor virus were detected in the DNA of all five lines, indicating that they were infected. The DNA of the five hyperplastic lines contained more EcoRI and BamHI mouse mammary tumor virus proviral DNA fragments than did DNA from normal organs, suggesting that the hyperplastic tissues were composed of more homogeneous cell populations than was lactating mammary gland. Each hyperplastic line had unique and reproducible BamHI and EcoRI restriction (integration) patterns which were stable over as many as seven transplant generations. Three sublines, which originated from the same hyperplastic alveolar nodule, had unique integration patterns but also shared several fragments. On the basis of these observations, we propose that mouse mammary "hyperplasias" are clonal dominant premalignant neoplasms.

¹ Supported by USPHS Contract NO1-CP-61013 from the Virus Cancer Program, Division of Cancer Cause and Prevention, National Cancer Institute and by USPHS Grant 5R01-CA 21454 from the National Cancer Institute.

² To whom requests of reprints should be addressed.

³ Present address: Department of Microbiology and Immunology, School of Medicine, University of Washington, Seattle, Wash. 98195.

Received 12/ 1/80. Accepted 4/22/81.

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