Relative Metabolic Activities of Normal and Tumorous Liver Nucleoproteins Indicated by Radiophosphorus. ∗

Abstract

The observations that tumors are high in arginase 1 and mono- and polynucleotidase 2 activities, and recent studies with radiophosphorus, 3 4 indicate rapid metabolism of the nuclear substance of neoplastic tissues. However, in these experiments, except those comparing lymphoma with normal lymph node, 4 it has been necessary to contrast cancer cells with various kinds of normal cells of different types. The liver carcinoma which can be produced by feeding azo dyes 5 is admirably suited to such experiments since the analogous normal tissue is readily available.

In Experiment I three groups of stock albino rats were used, one receiving a semi-synthetic diet (dextrin 79, casein 10, butter 5, salts 4, yeast 1, cod liver oil 1), another receiving in addition 0.06% dimethylaminoazobenzene (DAAB), and the third receiving 10% whole dried liver in addition to the basal ration and the azo dye. In Experiment II two groups of stock albino mice were used, one receiving a stock diet, 6 and the other in addition 0.05% p-aminoazotoluene (AAT). The rats were kept on the diet for 5 months and the mice for 7 months before the experiments, at which time all the animals receiving the azo dyes but no liver had developed hepatomata. Of 10 rats receiving both the azo dye and whole liver, only one developed liver tumors, and was discarded.

Each animal received subcutaneously 0.5 cc of a neutral radiophosphate solution. After 24 hours the animals were killed and the livers extracted 2–3 times with cold 0.01–2 N NH₄OH. The entire protein fraction was precipitated with cold trichloracetic acid, and the precipitate washed several times each with cold dilute trichloracetic acid, acetone, alcohol at 70°, and ether, in order to remove all non-nucleic phosphorus. The residue was then wet-ashed, the total phosphorus determined colorimetrically, and the radioactivity measured with a Geiger-Müller counter.