Radiation-Induced Changes in Tissue Nucleic Acids: Release of Soluble Deoxypolynucleotides in the Spleen

The hematopoietic tissues are among the most radiosensitive tissues in the mammalian organism. It has been known for many years that marked involution of spleen and bone marrow occurs after whole-body exposure to penetrating ionizing radiations in the lethal and sublethal dose range (1, 2). This process has been shown to be accompanied by marked losses of deoxyribonucleic acid (DNA) from these tissues (3, 4), indicating that there is an actual loss of cells. It is evident that the observed effects are related to the inhibition of incorporation of labeled precursor compounds into the DNA of hematopoietic tissues after whole-body X-irradiation (5-7). Furthermore, there is a considerable experimental literature which suggests that DNA may be a primary locus of action of ionizing radiations on biological systems (8-10). These considerations, coupled with experimental data which relate regeneration of the spleen and bone marrow to recovery and survival after acute radiation injury in mammalian organisms (4, 11, 12), point up the need for information on the early biochemical events involving the loss of nucleic acids from hematopoietic tissues after exposure to radiation. Recent advances in our knowledge of the state and the mode of chemical combination of DNA in the cell as nucleoprotein (13-15) have made feasible a direct biochemical attack on this problem. The present report involves a study of the changes in deoxyribonucleic acid content of mouse spleen during the first few hours after lethal whole-body X-radiation exposure, as well as later. Particular emphasis has been placed on alterations in the state of combination of DNA with protein under these conditions. A new scheme of chemical fractionation of the spleen has been employed which makes possible