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Cytogenetic Evidence for Gene Amplification in Mouse Skin Carcinogenesis¹

The University of Texas System Cancer Center, Science Park, Research Division, Smithville, Texas 78957 [C.M.A., C.J.C., J.O., A.J.P.K-S., T.J.S.], and Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20205 [S.H.Y.]

Using our recently developed methodology for cytogenetic evaluation of solid tumors, we analyzed the occurrence of double minutes (DM) in chemically induced mouse skin carcinomas and papillomas. These studies revealed that DM were observed in 10% of the squamous cell carcinomas and in none of the papillomas screened. In addition, we analyzed four cell lines derived from mouse skin papillomas and one spontaneously transformed mouse epidermal cell line. The presence of DM was a consistent feature in all the studied cell lines. In the papilloma cell lines, the degree that DM occurred correlated with the cell line's capacity to form malignant tumors in immunosuppressed mice. DM were also observed in direct chromosomal preparations from tumors induced by one of the papilloma cell lines. Homogeneously staining regions were also present in metaphases from the spontaneously transformed cell line. We have shown here, for the first time, DM and homogeneously staining regions in mouse skin tumors and transformed cells derived from mouse skin. Since DM and homogeneously staining regions are the cytogenetic equivalents of gene amplification, which is a mechanism of increased expression of normal or altered gene products, these findings may play a relevant role in mouse epidermal carcinogenesis.

¹ This research is supported by the Sid W. Richardson Foundation and Grants CA 34962 and CA 34521.

² To whom requests for reprints should be addressed.

Received 12/10/85. Revised 3/18/86. Accepted 3/25/86.