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The Stimulatory Effect of a Serum Factor on DNA and Protein Synthesis in Hepatoma Cells¹

Department of Anatomy and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

A serum factor present in normal rat serum disappears from the serum of hepatoma-bearing rats. This disappearance is dependent on the size of the hepatoma and is detected by polyacrylamide gel electrophoresis. Diminished amounts of the factor can be detected about 10 days after transplant of Morris hepatoma 7777, but total disappearance as judged by polyacrylamide gel electrophoresis takes about 4 to 5 weeks, when the tumor weight starts to surpass liver weight.

Evidence is provided that the factor influences metabolism of hepatoma cells but has only slight effects on liver cells. Hepatoma cells in suspension incorporate less leucine-³H and thymidine-³H with serum from hepatoma-bearing animals as a medium supplement than with normal rat serum. Liver cells do not distinguish between the 2 sera. Addition of purified factor to serum from hepatoma-bearing animals increases incorporation of label into hepatoma cells, and levels of incorporation approach those found with normal rat serum as a medium supplement. Addition of the factor to normal rat serum does not enhance incorporation. The factor by itself, without any serum added to the medium, supports incorporation of label into hepatoma cells. Liver cells do not respond to the factor as do hepatoma cells. Only the factor by itself has an effect on the incorporation of thymidine-³H into liver cells, as compared to incorporation without any serum. The mode of action of the factor is presently being investigated.

¹ This work was supported by USPHS Grant 2 R01 CA11637-04A1 PHRB.

Received 5/16/74. Accepted 7/23/74.