INHIBITION OF UPTAKE OF L-ARGININE-U-C¹⁴ INTO NUCLEAR PROTEINS BY 5-BIS (2-CHLOROETHYL) AMINOURACIL

¹ Department of Pharmacology, University of Illinois, College of Medicine, Chicago, Illinois

At various time intervals following the administration of 1 to 4 mg/kg of 5-bis (2-chloroethyl) aminouracil to rats bearing the Walker 256 carcinosarcoma, 7.5 µc of L-arginine-U-C¹⁴ was injected. An hour later, the tissues were excised and the specific activities of the proteins of the intracellular fractions were determined.

The data obtained provide in vivo evidence that the primary site of action of the aminouracil mustard is in the nucleus. The drug particularly affects the systems which are involved in the biosynthesis of the acid insoluble nuclear proteins. This intracellular selectivity of action was demonstrated for the Walker tumor and the spleen which are the biological sites of inhibitory action of this compound. The effect on the spleen was more marked than the effect on the tumor. The drug had virtually no effect on the incorporation of the labeled isotope into the cytoplasmic proteins of the tissues studied.