The anthracyclines have several effects, and their specific mode of action is unclear.

There are direct effects at the cell surface and also on signal trans-duction, specifically activation of protein kinase C-mediated cell signalling pathways. The role of these actions in mediating anthra-cycline cytotoxicity is undefined.

Their ability to undergo reduction to highly reactive compounds and generate free radicals has clinically important implications. Characteristic cardiotoxicity of anthracyclines appears due to the generation of free radicals in the heart where defence systems are less active.

The major target of anthracyclines is the enzyme topoisomerase II. During cell division topoisomerase II binds to DNA forming a 'cleav-able complex' that makes transient 'nicks' in DNA, allowing torsional strain in DNA to be released, after which strands rejoin. Anthra-cyclines bind to the cleavable complex, disrupting this process, leading to DNA strand breaks and cell death.

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