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Comparative High-Resolution Electrophoresis of Tumor Histones: Variation in Phosphorylation as a Function of Cell Replication Rate¹

Department of Biochemistry, University of Iowa, Iowa City, Iowa 52240 [R. B., M. B., R. C.], and Department of Biochemistry, Howard University, Washington, D. C. 20001 [H. P. M.]

We have examined the lysine-rich histones from a series of rat and mouse tumors by high-resolution gel electrophoresis and have found a positive correlation between the rate of tumor growth and the extent of lysine-rich histone phosphorylation. This correlation has been found in tumors of a variety of tissues from both rats and mice, further supporting the idea that F1 phosphorylation is an event primarily associated with the process of cell replication. The linear correlation between tumor growth rate and the extent of histone phosphorylation, coupled with cell-cycle data from two of the rat hepatomas, has led to the proposal that the observed increase in F1 phosphorylation in the rapidly dividing tumors results from (a) an increase in the fraction of cells actively dividing in the tissue and (b) a decrease in the relative proportion of the cell-cycle time occupied by the G₁ phase of the cell cycle.

¹ This work was supported by USPHS Grants CA-10871 and CA-10729, by American Cancer Society (Iowa Division) Grant P-451, and by United States Department of Health, Education, and Welfare Grant AI-07690-06.

² Recipient of USPHS Research Career Development Award GM 46410.

Received 1/27/72. Accepted 4/14/72.