The effects upon cellular
DNA and cytotoxicity produced by the
anthracyclines 5-iminodaunorubicin and
Adriamycin were studied in mouse
leukemia L1210 cells.
5-Iminodaunorubicin produced
protein-concealed
DNA strand breaks as measured by alkaline elution as had other
intercalators including
Adriamycin.
5-Iminodaunorubicin produced DNA breaks more efficiently than did
Adriamycin despite a lower potency for
free radical formation. Many of the
5-iminodaunorubicin breaks measured in this assay may arise from apposed single-strand breaks (i.e., double-strand breaks).
5-Iminodaunorubicin produced breaks which disappeared within 1 to 2 hr following
drug removal and were in this way similar to the breaks produced by the
acridine intercalator 4'-(9-acridinylamino)methanesulfon-m-anisidide.
Adriamycin produced more persistent breaks. Despite similarities in the kinetics of break disappearance,
5-iminodaunorubicin produced greater cytotoxicity than did 4'-(9-acridinylamino)methanesulfon-m-anisidide when compared at doses producing equal single-strand or double-strand breaks. Differences in the ratio of single-strand breaks to double-strand breaks and the associated cytotoxicity for
5-iminodaunorubicin and 4'-(9-acridinylamino)methanesulfon-m-anisidide indicate that a different mechanism is probably involved in the DNA break production by each agent. Differences between the cytotoxicity associated with the DNA break production by two agents with similar break disappearance kinetics indicate that
intercalator-induced DNA breaks cannot be a uniformly lethal DNA lesion.