Contrasts in the actions of protein antibiotics on deoxyribonucleic acid structure and function

Abstract

The protein antibiotics neocarzinostain (NCS), macromomycin (MCR), and auromomycin (AUR), which is closely related to MCR, have been compared for their in vitro and in vivo actions on deoxyribonucleic acid (DNA). NCS, markedly stimulated by 2-mercaptoethanol, is much more active in inducing strand scissions in superhelical pMB9 and linear duplex lambda DNA than AUR, which is slightly inhibited by 2-mercaptoethanol. Purified MCR, even at very high levels, does not give any significant amount of cutting with either DNA substrate. 2-Propanol stimulates the activity of NCS but inhibits that of AUR. On the other hand, the antioxidant alpha-tocopherol strongly inhibits DNA breakage by both drugs. The intercalating drugs ethidium bromide, daunorubicin, proflavin, and actinomycin D at low concentrations inhibit DNA scission by AUR. The levels of intercalators required to inhibit NCS activity to comparable levels are about 10 times higher than those for AUR. Although MCR has virtually no in vitro DNA cutting activity, it is, like AUR and NCS, cytotoxic, as measured by the inhibition of DNA synthesis and induction of DNA strand breakage in HeLa cells.