The mechanism of action of
auromomycin, a new
tumor-inhibitory
antibiotic, was studied in a growing culture of mouse lymphoblastoma L5178Y cells and with isolated
viral DNA.
Auromomycin prevented growth of L5178Y cells completely and irreversibly at
antibiotic concentrations higher than 0.03 microgram/ml.
DNA synthesis was preferentially inhibited by the
antibiotic, whereas
RNA and
protein syntheses were not significantly affected. In synchronous cultures of L5178Y cells, results 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 L5178Y cells was observed by an analysis of alkaline
sucrose gradient centrifugation. In vitro, the
antibiotic also induced strand breaks in linear duplex T-7 phage
DNA and in the supercoiled circular duplex of SV40
DNA.
2-Mercaptoethanol neither enhanced nor was required for strand scission of isolated
DNA by
auromomycin. These data indicate that the mechanism of the antitumor activity of
auromomycin is different from that of
bleomycin,
neocarzinostatin, or macromomycin.