Studies of Hypoproteinemia in Cancer ・Experimental Studies on the Mechanism of Hypoalbuminemia in Tumor-Bearing Rats.

Of various phenomena characteristic of cancer cachexia commonly observable in various malignancies, the derangement in protein metabolism distinctive to cancer has been explained by the nitrogen trap theory, after reported observations that an energetic utilization of proteins, especially of plasma albumin, as the material for the tumor growth, is being carried out in tumor tissue. n the present study, Yoshida sarcoma, which is known to be of a considerably high grade of malignancy, was subctaneously transplanted into Donryu strain male rats, and distribution of albumin throughout the body of the tumor-bearing rats was studied using 131I-labelled albumin and also using an immunochemical method of albumin quantitation. The daily dynamic changes of albumin distribution in organs and tissues were thus studied. In addition, 14C-labelled rat albumin was prepared and used in an incubation study in attempts to demonstrate the process of direct utilization of albumin by tumor tissue slices for the synthesis of tissue proteins. 1) Rat albumin was isolated in a purified form using the methods of ammonium sulfate fractionation, starch block electrophoresis and gel filtration. The purified preparation, after being checked for purity by cellulose acetate electrophoresis and immunoelectrophoresis, was used for preparing an anti-rat albumin rabbit serum. A satisfactory reproducibility was obtained by an immunochemical method of albumin quantitation using the antiserum incorporated in agarose plates, when the antiserum concentration was 5 mℓ/100 mℓ and the albumin concentrations of samples to he tested were between 10 and 180 mg/100 mℓ 2) After Yoshida sarcoma transplantation, a slight increase of circulating plasma volume, together with a decrease of serum albumin, was found to occur. Serum albumin concentration at five days after transplantation was the lowest of values throughout the course, and a slight re-elevation was encountered at six days after transplantation. 3) The decrease of total exchangeable albumin found in the initial and intermediate stages of tumor-bearing condition was mainy due to a decrease of intravascular albumin. On the other hand, the increase of total exchangeable albumin found in the terminal stage was mainly due to an increase of extravascular albumin. 4) In the initial stage after tumor-transplantation, there was a temporary decrease of the albumin content of the liver tissue, which subsequently recovered to a value approximately similar to the pre-transplantation value. The decrease of intravascular albumin encountered during this period was only slight, when compared with the controls, with a sharp decline to the lowest value found thereafter at five clays after transplantation. 5) Observation of the distribution of albumin in organs and tissues revealed that approximately 70% of the total body albumin was present in the "carcass" as extravascular albumin, and approximately 18% was represented by intravascular albumin. The liver contained approximately 5%, the kidneys and gastrointestinal tract 1% each, the spleen 0.2%, and other organs 3.4%. 6) With exceptions of the liver, tumor and the gastrointestinal tract, the albumin contents of the remaining organs and tissues, especially of carcass, had a tendency to decrease from the initial stage, demonstrating the nitrogen trap mechanism of cancer cachexia. 7) The rapid increase of extravascular albumin and the recovery of decreased intravascular albumin observed in the terminal stage, together with the increase of albumin in the gastrointestinal tract in this stage, may suggest a decline of physiologic albumin catabolism, represented by the enterohepatic cycle, and a decline of albumin utilization by the tumor tissue. 8) The observation that the albumin content of the tumor in the relatively early stage of tumor growth was as high as 9.83±1.78 mg/g wet tissue weight may suggest that the rapidly growing tumor tissue preferentially utilizes plasma albumin as the a