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THE MAJOR RESFARCH ACTIVITIES IN ‘IHE TRACER CHEMISTRY SEICTIO?? OF TRE DIVISION OF RADIOlDGY AND BIOPHYSICS The effects of chronic irradiation, and of sublethal acute irradiation seem t o be largely inthe direction of accelerating those involutional cmd degenerative processes, such as increased tendency to develop malignant disease, characteristic of aging i n the mammal. changes are associated with major alterations i n pratein metabolism. data provided by studies in this field are significant both i n providing criteria f o r the magnitude of such processes and, it is hoped, in providing thmugh new basic information clues that will make possible retarding, stopping, o r reversing of such normal o r abnormal involution, whether due to radiation, other toxic substances, o r more natural causes. by continuously pumping oxygenated blood through it has been used i n studies bearing on the”synthesis of the p+ma and l i v e r proteins i n normal and abnormal rats including experimental cirrhotics, experlmental diabetics, and carcinogen fed On the biochemical level such natural and pathological The technique of surgically removing the liver and maintaining f t alive The isolated perfused liver continues to be used i n extending our knowledge of the dominant role of the l i v e r i n the synthesis and metabolism of the plasma acetate, 8 - labeled lysine, and S35-labeled sulfate.A number of interesting observations have been made: and the plasma lipoproteins with the aid of carbon-lblabeled 1. A close physical and chemical association of the plasma lipids ( 8 lipoproteins) and the plasma mucoprotein fraction (particularly the alpha-one and alpha-two mucoproteins) has been found. the mucoproteins at a rate two t o five times greater than into the other protein 2. Labeled lysine is incorporated i n t o the alpha globulin fraction including 3. The catabolism of plasma and l i v e r proteins has been sham to give rise i n the isolate’d perfused liver to enough urea nitrogen t o account for almost all of the endogenous urea nitrogen produced by the i n t a c t rat (which corresponds in size to the rat supplying the liver for the perfusion). sparing action of the carbohydrates glucose and fructose and their related metabolites in the catabolism of l i v e r and plasma proteins is under way. A study of the nitrogen4. The remarkable increase i n the plasma mucoproteins after whole body radiation injury remains to be characterized w i t h respect to the particular mucoproteins which increase after radiation injury and the relation, if any, to the
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5 . The effects of glutamine, glutamic acid and ammonia (as ammonium carbonate) have been studied and compared w i t h respect t o their effects on urea synthesis, plasma and liver protein synthesis Glujp supplementation a remarkable depressant effect on the production of C O2 from L-lysine-6-C1td greatly enhances the incorporation of l y ~ ine - 6 - c ~ ~i nto plasma and liver proteins. 6. Unequivocal evidence has been obtsined for a direct action of insulin on the isolated perfused liver. demonstrate an effect of insulin on liver slice systems, we have been able t o clearly demonstrate that the perfused alloxan diabetic liver responds to insulin witha correction of metabolic defects in lipid synthesis and carbohydrate ' cerning the effects of carbohydrate supplements, fasting, and insulin on p l a s m and liver cholesterol synthesis and ketone body formation. I n contrast t o the failure of other investigators t o A t the same time these studies have yielded valuable information'conA detailed study of the respective oxidative abilities of the liver with respect t o amino acids and of the non-hepatic tissues, i n particular the kidneyI is w e 1 under way. Preliminary data obtained w i t h regard to oxidative disposal little lysine, histidine, phenylalanine o r tryptophane. Further, that the nonhepatic tissues are capable of oxidizing glutamic acid as well as the liver and also oxidize leucine, isoleucine, and glycine to a comparatively significant extent ( 5 t o 12s of the dose). $4-la$eled amino acids reveal that the non-hepatic tissues oxidized very The --i n vitro achievement of positive nitrogen balance i n the isolated perfused fiver has been effected in normal rat livers only by the simultaneous we of a complete amino acid mixture with a large supplement of glucose o r fructose along w i t h insulin and growth hormones (Miller, Burke, Haft, 1956). The use of this combination i n the study of nitrogen balance and net protein synthesis remains t o be studied i n the isolated livers from tumor-bearing rats, diabetic rats, and The nature of an hepatic factor favoring the abnormal synthesis of protein Attempts to devise an --i n v i t r o systemby the Walker tumor is being investigated. for testing stiumulation of tumor protein synthesis by a l i v e r factor have led us to develop a method for growing the Walker tumor in tissue culture. inducing growth of the Walker tumor as an "ascites tumor," w e have eliminated the troublesome complication of fibroblasts which overgrew the tumor cells in tissue culture. Now, witha "pure" growth of Walker tumor cells, we are ina position t o explore the effects of various liver fractions on tumor growth. plan also to study overall protein and amino acid metabolism in the isolated growing Walker tumor cells; i n particular it will be possible to determine t o what extent, if a t all, the Walker tumors can directly utilize homologous plasma proteins f o r tumor protein synthesis.