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Selective Inhibition by Sorbylhydroxamic Acid of Deoxyribonucleic Acid Synthesis in Ehrlich Ascites Tumor Cells¹

Veterans Administration Hospital and Department of Pharmacology, Medical College of South Carolina, Charleston, South Carolina 29403

Sorbylhydroxamic acid (SOHA) inhibited the incorporation in vitro of thymidine into deoxyribonucleic acid in Ehrlich ascites tumor cells, with no appreciable effect on the incorporation of uridine into ribonucleic acid or of L-leucine into protein. Hexanoylhydroxamic acid, devoid of the conjugated double-bond system, had no such activity. The concentration of SOHA conferring 50% inhibition of DNA synthesis was approximately 6 x 10^-4 M. Inhibition was almost totally abolished when the cells were washed free of the compound but was only partially antagonized by supplementing the medium with a mixture of deoxyribonucleosides; this latter was interpreted as indicating that only part of the inhibitory action may be attributed to suppression of ribonucleotide bioreduction. No conversion by SOHA of intracellular DNA to an acid-soluble state was demonstrated. Electron microscopy of SOHA-sensitive bacteria grown in the presence of the inhibitor yielded cytological evidence of a reduced rate of DNA synthesis which was compatible with the biochemical data. A moderate reduction of the rate of development of Ehrlich ascites tumor cells in vivo was demonstrated at dosages which closely approximated toxic levels. Caution was suggested in utilization of this hydroxamate as a food preservative.

¹ Aided by NIH Grant GM-13958.

Received 3/21/69. Accepted 5/ 2/69.