Activation of sodium cyanate for selective inhibition of protein synthesis in cultured tumor cells.
Sodium cyanate, a selective inhibitor of protein synthesis in animal tumors in situ, has no comparable effect when added to tumor cells in culture. However, a rapid inhibition of protein synthesis in cultured tumor cells can be achieved by reaction of cyanate with the drug-metabolizing system of liver microsomes. Procedures are described for the induction, preparation, and testing of an active cytochrome P-450 fraction which converts cyanate to a short-lived dialyzable metabolite that selectively inhibits amino acid incorporation in tumor cells without a corresponding effect on protein synthesis in normal cells. The suppression of tumor protein synthesis is not due to a general toxicity reaction because thymidine incorporation into the DNA of tumor cells is not inhibited by the cyanate metabolite. When HeLa cells are exposed to sodium butyrate, a substance reported to suppress the malignant phenotype in several tumor cell lines, they lose their sensitivity to the cyanate metabolite. Chick fibroblasts which are normally insensitive to the cyanate metabolite become cyanate sensitive after transformation by the Schmidt-Ruppin strain of the Rous sarcoma virus.
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D001358:Avian Sarcoma Viruses; D001711:Biotransformation; D002087:Butyrates / Q000494:pharmacology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D003110:Colonic Neoplasms / Q000378:metabolism; D003485:Cyanates / Q000378:metabolism*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism*
D002087:Butyrates; D003485:Cyanates; D009363:Neoplasm Proteins