SOME ASPECTS OF THE DESOXYRIBONUCLEASE ACTIVITIES OF ANIMAL TISSUES

Abstract

It has been found that many animal tissues contain "acid" desoxyribonucleases with pH optima near 5.2. A chemical method for the determination of this activity is described. The pancreatic desoxyribonuclease crystallized by Kunitz and shown to have a neutral pH optimum occurs in the pancreas together with the "acid" enzyme, but only the "neutral" enzyme occurs in the pancreatic juice. The ratio of "neutral" to "acid" DNAase activities in the pancreas is greater than 200, but in all other tissues examined there is no appreciable concentration of the neutral enzyme. It is concluded that neutral DNAase, like trypsin or lipase, has a digestive function. Some problems in the activation of the secretory enzyme in neutral pancreatic extracts are described. This activation can be interpreted in terms of a specific inhibitor or an inactive form of the enzyme. A comparison of the "acid" DNAase activities of different organs of the calf, horse, chicken, mouse, and rat indicates a possible connection between the DNAase concentration of a tissue and its capacity for proliferation or regeneration. However, the comparative DNAase activities of fetal and adult tissues do not support the view that DNAase function is limited to some simple role in the mechanics of cell division. Studies on the incorporation of glycine-N15 into the desoxypentose nucleic acids of avian red cells, and mouse liver, pancreas, and kidney show that the N15 uptake into the DNA of the chromosome is most rapid in tissues with high DNAase concentrations. No N15 incorporation is observed in the DNA of avian red cells, which have negligible concentrations of the enzyme. The analyses of tissues and nuclei isolated in non-aqueous media show that the bulk of the enzyme occurs in the cytoplasm of the cell, and that nuclear concentrations vary from tissue to tissue. A theory relating the DNAase activity of the cell to its over-all desoxypentose nucleotide metabolism is discussed. No evidence has been found for the presence of inhibitors of the "acid" DNAase in animal tissues.