Physicochemical Alterations in Spleen Deoxyribonucleoprotein after in Vitro X-Irradiation with 850 R

Abstract

It is generally recognized that the dose of ionizing radiation needed to elicit marked biological effects including lethality in laboratory mammals is far smaller than that required to produce demonstrable effects when chemical compounds, or complexes isolated from tissues, are irradiated in vitro. The resolution of this enigma would appear to involve some fundamental aspects of the mechanism of action of ionizing radiations on biological systems. If a one-to-one stoichiometry between the number of ions produced by a given dose of radiation and the inactivation or chemical alteration of a corresponding number of molecules in a cell isassumed, it can be shown that only a very small fraction of the total number of molecules in a cell are directly affected (1). As an alternative to the assumption of a random process of molecular inactivation by the ionization, one is led to the concept that the primary biochemical event in the cell involves an alteration or inactivation of intrinsically radiosensitive molecules or molecular sites, present in limited numbers, and involved in functions essential to the life of the cell, or its progeny. The possibility that the deoxyribonucleic acid macromolecules, localized in the chromosomes of the cell nucleus, might be the primary biochemical locus of action of ionizing radiation has received serious consideration from many workers (2-5). Such considerations follow from a large number of experimental observations which have focused attention on the cell nucleus (6-8) as the site of biological damage induced by ionizing radiations. Indeed, radiation effects such as the inhibition of mitosis, induction of chromosome aberrations and the inhibition of new formation of deoxyribonucleic acid (DNA) are most pronounced in tissues possessing high