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Correlation between the Detection of Specific Mouse Mammary Tumor Proviral Sequences and the Presence of Pulmonary Metastases in Mice Bearing Spontaneous Mammary Tumors¹

Laboratory of Viral Carcinogenesis, Division of Cancer Cause and Prevention, National Cancer Institute, NIH, USPHS, United States Department of Health, Education and Welfare, Bethesda, Maryland 20205 [W.D., J.S.], and Department of Pathology, University of California School of Medicine, Davis, California 95616 [R.D.C., J.K.L.]

Pulmonary metastases in C3H/He mice bearing spontaneous mammary tumors were detected and characterized by histological criteria and immunocytochemical staining for mouse mammary tumor virus antigens. The same lungs containing metastases were also positive when assayed for a specific subset of mouse mammary tumor virus proviral DNA sequences. These sequences, termed tumor-associated sequences, have previously been shown to be present in the DNA of spontaneous mammary tumors that arise before 1 yr of age in C3H/He mice but are absent in DNA's of apparently normal tissues of C3H/He mice. Reconstruction experiments demonstrated that the nucleic acid hybridization method will detect at least one mammary tumor cell/250 lung cells. While DNA from 13 lungs of apparently normal C3H/He mice did not contain sequences homologous to mouse mammary tumor virus tumor-associated-sequence RNA, DNA from lungs of 9 of 12 C3H/He mice bearing spontaneous mammary tumors did contain these sequences. Since the entire DNA content of the lung can be assayed as one sample, the hybridization method minimizes false negatives resulting from histological analysis of random biopsy sampling. The hybridization procedure described here thus represents a sensitive and quantitative element as an adjunct for the detection of micrometastatic lesions in mice bearing viral-mediated spontaneous mammary carcinomas.

¹ This work was supported in part by Contracts N01-CP-43223 and N01-CP-61013 of the National Cancer Institute.

² To whom requests for reprints should be addressed, at Building 37, Room 1B19, National Cancer Institute, NIH, Bethesda, Md. 20205.

Received 12/27/79. Accepted 3/28/80.