The objectives of the program are to identify, isolate, and characterize the action of non-histone chromosomal proteins influencing tumor growth using transplanted hepatomas as a model system. It is proposed to study the influence of growth regulating agents on the synthesis of non-histone chromosomal proteins. The proteins will be extracted from nuclei by saline extraction and further resolved by isoelectric focusing. The relationship of protein synthesis to growth rate will be compared in liver and hepatomas. Purification will be attempted of non-histone chromosomal proteins whose concentration appears related to growth rate. Particular attention will be directed to proteins which bind the cyclic nucleotides, 3'5'-cyclic AMP and 3'5'-cyclic GMP. The tissue distribution of cyclic nucleotides and their association with non-histone chromosomal proteins will be investigated. In order to test the growth regulatory properties of isolated proteins, their influence on cellular proliferation will be examined after their administration as exogenous agents.