Platinum–DNA adduct (carboplatin-induced)

Carboplatin is a platinum-based chemotherapeutic agent that exerts its anti-cancer effects primarily by forming covalent adducts with DNA. These platinum–DNA adducts include monoadducts, intrastrand crosslinks (links within a single DNA strand), and interstrand crosslinks (linking the two complementary DNA strands). Interstrand crosslinks are particularly cytotoxic because they prevent the separation of DNA strands needed for replication and transcription, ultimately resulting in cell cycle arrest and apoptosis. Although these lesions occur at lower frequency than intrastrand crosslinks, their repair is significantly more complex and failure to repair them leads to cell death. The response to and repair of these crosslinks underlie the therapeutic effectiveness of carboplatin in various cancers, as well as the development of resistance and some of its dose-limiting toxicities.

Other names

DNA interstrand crosslink (ICL) (carboplatin-induced)carboplatin–DNA crosslinkplatinum-DNA crosslinkcarboplatin adduct

Covalent binding of platinum to DNA (mainly N7 of guanine and adenine) Formation of monoadducts, intrastrand and interstrand crosslinks (the latter are highly cytotoxic) Inhibition of DNA strand separation, blocking replication and transcription Induction of cell death (apoptosis) via irreparable DNA damage