The phosphorylation of histones in rat liver undergoing malignant transformation.

The incorporation of inorganic phosphate into H1-histones of rat liver was stimulated after the repeated s.c. administration of diethylnitrosamine. This stimulation was observed as early as after the fifth daily injection of the carcinogen and amounts to approximately 3 times the control value on the 60th day of the experiment. The effect was reversible when the application of the carcinogen was not extended beyond 4 weeks. A correlation was observed between these phenomena and alterations in the morphological structure, although the latter required a higher amount of single doses before the first signs of a forthcoming malignant transformation were seen. There was a difference in distribution of phosphate between the individual phosphorylation sites of the H1 molecule as compared to stimulated phosphate incorporation induced by adenosine cyclic 3':5'-monophosphoric acid or liver regeneration. The stimulated phosphorylation was not due to the inflammatory action of the carcinogen.