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Comparative Studies with Three Antibiotics Binding to Deoxyribonucleic Acid

Departments of Microbiology and Biochemistry, The Upjohn Company, Kalamazoo, Michigan 49001

ABSTRACT

The effects of the three antibiotics U-12,241, nogalamycin, and U-20,661 on (i) deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis in KB cell cultures and cell-free systems of bacterial and mammalian origin and on (ii) oxidative phosphorylation in rat liver mitochondria were compared. Nogalamycin and U-12,241 inhibited RNA synthesis more strongly than DNA synthesis in all test systems. Antibiotic U-20,661 inhibited DNA and RNA synthesis equally in whole mammalian cells and their corresponding cell-free systems. The RNA polymerase from Escherichia coli, however, was at least 100 times more sensitive to U-20,661 than was the DNA polymerase. U-12,241 caused significant uncoupling of oxidative phosphorylation in mitochondria.