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In Vitro Growth Control Phenotypes of Transformed Rodent Cells prior to and following Tumorigenesis¹

Department of Cellular, Viral, and Molecular Biology, University of Utah and Research Service, VA Medical Center, Salt Lake City, Utah 84148

² To whom requests for reprints should be addressed, at VA Medical Center, 500 Foothill Drive, Salt Lake City, Utah 84148.

A number of virus and chemical carcinogen-transformed cell lines were generated in tissue culture and analyzed for growth control phenotypes prior to and following tumorigenesis in appropriate hosts. The cell lines include those of mouse, rat, human, and Syrian hamster, transformed by papovaviruses and adenoviruses (DNA) or murine (RNA) tumor viruses. Cell lines were assayed for: (a) multinucleation or uncontrolled nuclear division (UND⁺) and uncontrolled DNA synthesis in cytochalasin B (CB) medium; and (b) the continuation of DNA synthesis in media containing reduced (0.5%) amounts of serum. All or nearly all lines of DNA virus transformants exhibited UND⁺ and high frequencies of DNA-synthetic cells in CB medium. Two lines of SV40-transformed hamster cells also showed UND⁺ following tumorigenesis in weanling hamsters. In addition, DNA virus transformants showed the ability to continue DNA synthesis unabated in low-serum medium. In contrast, the mouse sarcoma virus (MSV)-transformed lines exhibited varying degrees of controlled nuclear division and reduced DNA synthesis in CB medium, both prior to and following tumorigenesis. However, the reduction in DNA-synthetic cells was often not as great as that found in untransformed cells. Results similar to the RNA virus transformants were observed with hamster cells transformed by chemical carcinogens. Nearly all of the MSV-transformed lines showed significantly reduced levels of DNA synthesis in low-serum medium as was found in untransformed cells. One cell line, KA31, was followed through three consecutive in vivo tumorigenic passages, but these cells did not acquire UND+ or the ability to continue DNA synthesis in low-serum medium. These results suggest that many MSV- and carcinogen-transformed rodent cells exhibit transformation phenotypes at levels barely above those of normal cells and markedly less than those of DNA virus transformants, and yet they are tumorigenic.

¹ Supported by USPHS Grant CA 15141 and the Veterans Administration.

Received 2/16/82. Accepted 10/29/82.