Gisela Gerber

Studies on the Metabolism of Tissue Proteins: III. The Turnover of Soluble Proteins and Elastin Labelled with 14C proline and its Relation to Exposure to Total-body X-irradiation

SummaryRats were injected with proline-U-14C and exposed to total-body x-irradiation at various time-intervals thereafter. Proline was isolated from the soluble protein and elastin fractions of various organs and its specific activity determined. In most organs an increase in specific activity of proline of these two protein fractions was observed after irradiation. This was interpreted to mean either a lowered metabolic replacement or a loss of certain components from these protein fractions after irradiation. It is suggested that the decrease in specific activity observed in the spleen is correlated to changes in the cell-population in this organ after irradiation.

Studies of collagen turnover in lathyritic rats

Abstract Normal and lathyritic rats were injected with proline-U-C 14 and sacrificed at different time intervals after the injection. The neutral salt soluble and insoluble fractions of collagen were prepared from skin and bone, as well as total collagen from bone. Proline and hydroxyproline were isolated from all collagen fractions, and the respective specific activity was determined. On the basis of the data on incorporation and replacement of radioactivity in collagen and its fractions, it appears that the conversion of soluble to insoluble collagen is impaired in lathyrism.

Radiation-induced tissue breakdown. IV. The source of degraded amino acids in irradiated rats.

Summary1. An attempt was made to determine the source of excess 14C -labelled glycine and phenylalanine observed in ‘free’ metabolic pools of rats loaded with glycine-2-14C and phenylalanine-3-14C before irradiation.2. Tissues from various organs of irradiated and non-irradiated rats were fractionated into three protein fractions. Glycine, phenylalanine, tyrosine, serine and alanine were isolated from these fractions, and the respective specific activities were determined.3. Differences in specific activities were : decreased activity in muscle collagen and soluble-protein fractions of thymus and spleen; increased activity in soluble-protein fractions of liver and muscle; and variable changes in the activity of certain amino acids of the soluble-protein fraction of kidney.4. The significance of these changes is discussed in terms of known biological effects of radiation on cells and cellular metabolism.5. Muscle collagen seems radio-sensitive and its increased catabolism in irradiated rats could explain m...

Urinary Excretion of Several Metabolites in Persons Accidentally Exposed to Ionizing Radiation

BS>Urinary concentrations of creatine, beta -aminoisobutyric acid, pyrrole --carboxylic acid, and free hydroxyproline were determined in human subjects accidentally exposed to ionizing radiation at various time intervals after exposure. The range of doses of radiation varied from about 100 to 4000 rads. Increased concentrations of creatine and beta -aminoisobutyric acid in urine were found in most of the patients. Excretion of free hydroxyproline was decreased in the three most heavily exposed patients, whereas pyrrolecarboxylic acid was increased only in the fatally injured patient. (auth)

Creatine Metabolism after X-irradiation of Rats

Summary1. Creatine-2-14C was injected into rats at different times after x- or sham-irradiation.2. Muscle creatine and phosphocreatine, as well as creatine from blood, kidney and urine, were isolated and their respective specific activities determined. Urinary creatinine was also isolated and its 14C-activity determined.3. Coincident with the maximal excretion of creatine, the specific activities of muscle creatine and phosphocreatine decreased after x-irradiation.4. Immediately after injecting the x-irradiated rats with creatine-2-14C, the specific activity of urinary creatine increased, whereas that of creatinine decreased, but at a somewhat later time.5. It is postulated that defective utilization of creatine by muscle constitutes the cause of radiation-induced creatinuria.

The Catabolism of Nucleic Acids in the Rat: IV. The Replacement of Desoxyribonucleic Acid in the Irradiated Rat

Summary3H-thymidine was injected into rats three days before x- or sham-irradiation. Alterations in synthesis and replacement of DNA after irradiation were estimated on the basis of the changes in specific activity of DNA one to three days after exposure. Urinary β-amino isobutyric acid was also isolated in order to gain insight into radiation-induced changes of the specific activity in the precursor pools of DNA. On the third day the specific activity of DNA was lower in spleen and thymus and higher in the intestine of x-irradiated animals than that of sham-irradiated animals. The specific activity of β-amino isobutyric acid was somewhat higher on the first day and lower on the second and third day after x-irradiation than that of sham-irradiated rats. The significance of these findings in terms of inhibition of DNA-synthesis, alterations in DNA replacement and destruction of cells is discussed.

STUDIES ON THE METABOLISM OF TISSUE PROTEINS. II. INFLUENCE OF X- IRRADIATION AND STARVATION ON THE METABOLISM OF COLLAGEN

Rats were injected with proline-U-C/sup 14/ and exposed to total-body x irradiation at various time-intervals thereafter. Proline and hydroxyproline were isolated from collagen of various organs as well as from sub-fractions of skin collagen and their specific activity determined. From the changes in specific activity of proline and hydroxyproline observed after exposure it is postulated that more metabolically-active collagen is degraded and that the conversion of soluble to insoluble collagen is partially inhibited after irradiation. (auth)

The Mechanism of Radiation-Induced Creatinuria.

Summary Synthesis of creatine in X-irradiated, creatinuric rats was determined from the balance of creatine retained in the body and creatine and creatinine excreted in the urine. The rate of release of creatine from the muscle of irradiated rats was determined in irradiated rats which were injected with labeled creatine several days before exposure. The C14 activity of urinary creatine and creatinine reflecting the specific activity of “free” and muscle creatine, respectively, was determined before and after exposure. No alterations in rate of creatine synthesis or in its release from muscle were observed after irradiation. In agreement with previous studies, it was therefore concluded that radiation-induced creatinuria results from a failure of the muscle to utilize creatine synthesized at a normal rate.

THE CATABOLISM OF TISSUE NUCLEIC ACID. III. THE CATABOLISM OF RIBONUCLEIC ACID AFTER TOTAL-BODY X-IRRADIATION

SummaryThe catabolism of RNA after total-body x-irradiation of rats was studied by labelling RNA with glucose-U-14C. The specific activities of urinary ribosyl imidazole acetate, as well as of RNA of liver, intestine, muscle, and spleen, were determined after x- or sham-irradiation. After exposure to 1000 r, the specific activity of urinary ribosyl imidazole acetate was increased, whereas that of intestinal and muscle RNA was decreased. The specific activity of RNA in lymphoid organs was also decreased after exposure to 756 r.It is concluded that a radiation-induced increase in RNA catabolism is present mainly on the second and third day after exposure, primarily in intestine and muscle. In contrast, the starvation-induced increase in the catabolism of RNA occurs primarily in the liver and on the first day of starvation.

CREATINE METABOLISM AFTER X-IRRADIATION OF RATS. II. DIRECT AND INDIRECT EFFECT OF RADIATION.

Previous investigations in our laboratory (1, 2) have shown that the creatinuria observed in whole-body X-irradiated rats is caused by a defect in the ability of skeletal muscle to take up creatine from blood. Such an abnormality could be the result of direct damage to the muscle caused by the incident radiation or could represent an abscopal effect on the muscle mediated by some indirect mechanism other than the adrenal (3). In the present investigation, the direct and indirect action of radiation on creatine uptake by skeletal muscle has been assessed by comparing the ratio of the specific activity of urinary creatine to muscle creatine in X-irradiated and shielded muscle of rats receiving partial-body exposure prior to injection of creatine-l-C14.