Potentiation of the cytostatic effect of bleomycin on L5178y mouse lymphoma cells by pepleomycin.

Bleomycin (BLM) and pepleomycin (PEP) are two chemically related glycopeptide antitumor antibiotics which differ in their terminal residues only. Studying the growth-inhibitory potencies of BLM (clinical mixture), BLM-A2, BLM-B2 and PEP in the L5178y mouse lymphoma cell culture system, it was elucidated that the slopes of the dose-response curves at the ED50 concentration (around 1 microgram/ml) were steeper for PEP than for BLM. This result together with cytotoxicity determinations revealed a cytostatic action of PEP within a closer concentration range than BLM. Both drugs inhibit cell proliferation during S- and G2-phase. Given in combination, BLM and PEP inhibit cell proliferation in a highly significant synergistic way (FIC indexes: 0.25-0.46). This in vitro result, which might be of therapeutic importance, is correlated with differences on the molecular level. Determinations of the ratio between the number of single- and double-strand breaks in the DNA (the target molecule of the drugs) revealed a considerably lower value for DNA from BLM-treated cells (1.9:1) than for DNA from PEP-treated cells (13:1).