DNA Strand Scission in Vivo and in Vitro by Auromomycin1

The mechanism of action of aunomomycin, a new tumor inhibitory antibiotic, was studied in a growing culture of mouse lymphoblastoma L51 78Y cells and with isolated viral DNA. Auromomycin prevented growth of L5i 78Y cells completely and irreversibly at antibiotic concentrations higher than 0.03 pg/mI. DNA synthesis was preferentially inhibited by the anti biotic, whereas RNA and protein syntheses were not signifi cantly affected. In synchronous cultures of L5178Y cells, re suIts indicated that limited auromomycin-induced inhibition of DNA synthesis may occur independently of a much stronger inhibition of mitosis. In a short incubation period, a marked strand scission in cellular DNA of auromomycin-treated L5i 78Y cells was observed by an analysis of alkaline sucrose gradient centnifugation. In vitro, the antibiotic also induced strand breaks in linear duplex T-7 phage DNA and in the supercoiled circular duplex of SV4O DNA. 2-Mercaptoethanol neither enhanced nor was required for strand scission of iso lated DNA by auromomycin. These data indicate that the mech anism of the antitumor activity of auromomycin is different from that of bleomycin, neocarzinostatin, or macromomycin.