Our studies have focused on post-translational modification of chromosomal proteins in the nuclei of Walker-256 carcinosarcoma cells, and nuclei of other rat tissues. In addition to the previously described modifications of these proteins (acetylation, methylation and phosphomonester formation, we are concentrating on a new form of phosphorylation which leads to the formation of acid-labile phosphate linkages. We propose to describe in more detail the kinases for histones I and IV, which can be fractionated from the chromosomal non- histone proteins that should be rat cell nuclei. Phosphorylation of histone fraction I (the very lysine-rich) leads to the formation of an epsilon-phosphoryl amino lysine and phosphorylation of histone fraction IV leads to the formation of phosphohistidine in this molecule. Emphasis will be placed upon a possible biological role of this form of histone modification. We have further focused our studies on the formation and release into culture medium of mucopolysaccharides by normal fibroblasts, and by tumor cells (Walker-256 cells) in culture. Related to this project will be an attempt to learn when in the life cycle of the cell which mucopolysaccharides are laid down, and what, if any, differences exist in the pattern associated with normal and malignant cells. Finally, we are interested in the possibility that the rate and extent of mucopolysaccharide synthesis and sulfation may be regulated by exogenous molecules.