Primary Antimitochondrial Activity of the Cancer Drug Methylglyoxal Bis(guanylhydraz0ne) in Yeast Cells

Primary action of methylglyoxal bis(guany1hydrazone) (MGBG) on the yeast mitochondrial system was demonstrated by (1) selective inhibition of cell growth in non-fermentable medium, (2) blockage of mitochondrial synthesis of cytochromes aa, and b and (3) ultra-structural aberration. The drug caused extensive deletions in mitochondrial DNA detected by an increase in the frequency of the mitochondrial mutant petite but had little or no effect on cell viability. Growth inhibition by MGBG was antagonized by spermidine but neither the polyamine nor MGBG had any effect on growth inhibition by ethidium bromide. Strains showed no cross-correlation in their tolerance to MGBG and ethidium bromide