PROTECTION BY SELECTIVE AMINO-ACID SOLUTIONS AGAINST DOXORUBICIN-INDUCED GROWTH-INHIBITION OF ESCHERICHIA-COLI

1. Incubation of Escherichia coli with 0.7 mM doxorubicin in MBS-gluco se medium resulted in complete growth inhibition, an inhibition that w as blocked by placing specific amino acids (AA) in the medium. 2. The mechanism of protection by AA was similar to that reported previously for cells poisoned by hyperoxia and by paraquat, e.g. of 20 common AA, ten protect, ten do not and the branched-chair AA are among those req uired for inhibition. 3. Unlike hyperoxia and paraquot stringency whic h caused elevation of intracellular concentrations of guanosine tetrap hosphate (ppGpp), doxorubicin inhibition did not elevate ppGpp. 4. Con centrations of ppGpp were increased by isoleucine starvation as expect ed, and the subsequent addition of doxorubicin did not abolish that in crease; however, pretreatment with doxorubicin prevented the induction of stringency by isoleucine starvation. 5. This suggests that doxorub icin directly inhibits ppGpp synthesis or protein biosynthesis to leav e tRNA loaded as is the case with chloramphenicol.