Intracellular reduction of the cupric ion of bleomycin copper complex and transfer of the cuprous ion to a cellular protein.
The cupric ion of the bleomycin copper complex has been shown to be reduced and transferred to a cellular protein by the following mechanism: Bleomycin approximately Cu2+ leads to Bleomycin plus Cu+ X Cu+ plus M leads to M approximately Cu+. The intracellular reducing agents (X) are suggested to be sulfhydryl compounds, because their action is inhibited by N-ethylmaleimide. The active group of the cellular protein (M) that binds with the cuprous ion is suggested to be a sulfhydryl group. The action of the bleomycin copper complex in causing DNA fragmentation in cells can be explained by the mechanism presented in this paper. This mechanism in cells is also supported by the temperature dependency of the action of the bleomycin copper complex on cells.
D000818:Animals; D001761:Bleomycin / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D008970:Molecular Weight; D010084:Oxidation-Reduction; D011485:Protein Binding; D051381:Rats; D013696:Temperature; D013997:Time Factors
D001761:Bleomycin; D003300:Copper; D004247:DNA