Inhibition by Penicillamine of DNA and Protein Synthesis by Human Bone Marrow 1

Abstract

Summary

The sulfhydryl-containing amino acid penicillamine inhibited uptake of thymidine-³H, deoxyuridine-³H, and formate-¹⁴C into DNA of human bone marrow cells in vitro. Pencillamine inhibition of leucine-³H incorporation into protein was also inhibited; less inhibition of uridine-³H uptake into RNA was demonstrated. Significant inhibition was present with a concentration of penicillamine not much more than that presumed present in plasma of patients ingesting the drug. Penicillamine inhibition was not significantly affected by prior incubation of bone marrow cells with L-valine, iron, copper, zinc, pyridoxine, or pyridoxal phosphate.

The L-enantiomorph was more inhibitory than the d form.

These findings may help explain the inhibitory effects of penicillamine on animal tumors, and suggest possible value of this drug in chemotherapy of human neoplasms.