[Induction of single- and double-strand breaks in linear and superhelical DNA by phleomycin]

Phleomycin induced DNA breakage was investigated with superhelical Col. E1 DNA and linear T2 DNA as well. In both DNA-forms besides single-strand breaks direct double-strand breaks were produced by the drug. The double-strand breakage rate obtained after treatment with phleomycin, however, was considerably smaller than that found after bleomycin treatment. Whereas the single- and double-strand breakage rate in Col. E1 DNA showed a linear and nearly quadratic dependence on the phleomycin concentration, respectively, in T2 DNA the breakage rates increased faster than the first or second power of the concentration. This indicates various modes of drug-DNA interaction. Under nondegrading conditions a strong retardation of electrophoretic mobility was observed for all three topological isomers of Col. E1 DNA whereas the sedimentation behaviour remained unchanged. The in vitro effects (strand breakage) of phleomycin and bleomycin are compared with induction of chromosomal aberrations in human lymphocytes and oocytes of Drosophila melanogaster.