Modification Of Radiation Injury Research Articles

Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis

The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal 125I irradiation of normal brain, and to determine the effects of an intravenous infusion of alpha-difluoromethylornithine (DFMO) on those responses. Adult beagle dogs were irradiated using high activity 125I sources. Saline (control) or DFMO (150 mg/kg/day) was infused for 18 days starting 2 days before irradiation. At varying times up to 8 weeks after irradiation, brain tissues were collected and the cell responses in and around the focal lesion were quantified. Immunohistochemical stains were used to label astrocytes (GFAP), vascular endothelial cells (Factor VIII), polymorphonuclear leukocytes (PMNs; MAC 387) and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cellular responses were quantified using a histomorphometric analysis. After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. alpha-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm2 were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation injury may be possible by manipulating the response of normal cells to injury.

Overview of symposium: Chemical mechanisms in radioprotection

My brief is to discuss some of the facts that have emerged concerning chemical mechanisms of radioprotection. Like Dr. Phillips, I shall draw not only on information provided by speakers at this Symposium, but also, where appropriate, on information already available in the literature-information that is often overlooked by builders in their search for new principles. I shall not attempt to review each of the relevant papers presented: the authors make their 'own cases much better than I can anyway. I intend to confine my remarks to what I consider to be some important general principles. There is now a fascinating ring of reality in the progress towards a useful--and usable-radioprotector. The concepts of substances that influence immunological response, the induction of repair proteins, and the biological modifiers, all open up new areas of enquiry and illustrate clearly to me that the field of radioprotection is now undergoing a rapid metamorphosis. This Symposium is indeed timely. Dr. Phillips has made an interesting distinction between physiological and pharmacological mechanisms involving, for example, modification of radiation injury by exogenous substances, particularly those containing thiols. This is a useful and valid approach. To complement this, I shall address the problem from the standpoint of basic radiation chemical mechanisms, often flee radical in origin, and I shall certainly draw heavily on information derived from both chemical and biological studies with exogenous thiols. Of necessity, however, I must consider some aspects that Dr. Phillips alluded to in his first class of physiological mechanisms. I refer to the influence of changes in cellular levels on overall radiation damage, the interaction of sensitization and thiol protection, and the methods of influencing the yield of radiation-induced chemical lesions. Despite the current diversification in the radioprotector field, the study of substances that permit chemical repair of free radical radiation remains the major area of enquiry at all levels of biological complexity. The so-called oxygen fixation competition model first proposed over 30 years ago remains very much in vogue and figured prominently in several papers in this Symposium. The postulates that a free radical lesion induced by radiation (reaction 1) in a biologically important molecule, DNA for example, can be repaired by hydrogen transfer from appropriately located intercellular thiols (reaction 2). This reaction competes with an oxidation reaction in which f ixes the radical by peroxy-radical formation (reaction 3).

Modification of Radiation Injury in Blood, Bone Marrow, and Spleen by Long-Term Postirradiation Hypoxic Hypothermia

The effect of hypoxic hypothermia was investigated in mice at a body temperature of 25-30°C and atmospheric pressure of 250-300 mm Hg for 5.5 days after irradiation. These conditions shorten the mean survival time and increase the loss in body weight of irradiated animals. These conditions also delay the decrease in neutrophils and, to a lesser degree, the decrease in peripheral lymphocytes and erythrocytes as well as all elements of the bone marrow and spleen. A delay in the development of reparative processes in the germinal centers of splenic lymphatic nodules was also noted. During the first three days of hypoxic hypothermia the bone marrow and the spleen red pulp show an increase in the mitotic index. Hypoxic hypothermia stimulates ectopic erythropoiesis in the spleen red pulp in irradiated as well as nonirradiated animals. In irradiated animals the stimulation occurs particularly within the first 48 hours after irradiation. Symptoms of a lasting favorable effect of hypoxic hypothermia on the reparat...

Physical Factors and Modification of Radiation Injury. L. D. Hamilton

Previous articleNext article No AccessNew Biological BooksPhysical Factors and Modification of Radiation Injury. L. D. Hamilton PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Quarterly Review of Biology Volume 40, Number 2Jun., 1965 Published in association with Stony Brook University Article DOIhttps://doi.org/10.1086/404617 PDF download Crossref reports no articles citing this article.

Modification of radiation injury in rats through gastrointestinal tract shielding and bone marrow therapy.

The efficacy of postexposure administration of isologous bone marrow in preventing mortality was compared in whole-body x-irradiated rats and in animals exposed with three grossly different amounts of the gastrointestinal tract exteriorized and lead shielded. Survival was not enhanced by the therapy in animals which sustained severe intestinal radiation injury and died during the first postexposure week. However, significant protection was afforded by the treatment in animals in which the incidence of acute intestinal radiation deaths was reduced or virtually eliminated by intestinal shielding and deaths in the untreated controls occurred predominantly during the second postexposure week from bone marrow injury. The data demonstrate that bone marrow therapy is effective primarily in preventing deaths associated with radiation-induced damage to the hematopoietic tissue and not to the intestine, and hence its therapeutic value becomes limited as the prominence of intestinal injury increases with increasing radiation dosage in the whole-body irradiated animal.

The Effect of Bone Marrow Injection on the Incorporation of Formate-Carbon-14 into Deoxyribonucleic Acid Purines in X-Irradiated Rats

The establishment of the protective effect of intraperitoneal implants of spleen (1), of intraperitoneal or intravenous injection of spleen homogenates (2, 3), and of the administration of bone marrow suspensions (4-6) on otherwise lethally X-irradiated animals has stimulated interest in the mechanisms by which these preparations modify the lethal effect of X-radiation. Among early indications of radiation damage is the inhibition of incorporation of labeled precursor substances into tissue deoxyribonucleic acids (DNA) in Xirradiated laboratory animals. This effect was first demonstrated by Hevesy et al. (7, 8) with inorganic P32 and acetate-C14. An X-radiation dose of 800 r decreases also the incorporation of glycine-C14 into DNA and ribonucleic acid purines of rabbit bone marrow and of rat intestine (9). Previous studies in this laboratory have shown that protection against radiation death in mice (LD,oo dose) afforded by isologous spleen homogenate injection is accompanied by a reversal of radiationinduced inhibition of incorporation of C'4-formate into spleen and bone marrow nucleic acid purines (10) and by a recovery in the spleen DNA levels (11). The present experiments were designed to determine whether modification of radiation injury in rats by rat bone marrow (6) is similarly reflected in changes in nucleic acid metabolism in radiosensitive tissues. Specifically, the effect of injection of rat bone marrow on the incorporation of formate-C14 into DNA adenine and guanine has been studied in selected tissues of lethally X-irradiated rats.

Modification of radiation injury in the rabbit.

ConclusionsPostirradiation injection of mouse embryo cells or baby mouse liver or spleen cells enhances significantly the survival of rabbits exposed previously to 900 r total-body X radiation without producing an appreciable effect upon hematologic recovery as observed in the peripheral blood.