ABSTRACT
Cisplatin is a neutral inorganic, water-soluble, coplanar complex (Figure 6.1). e drug enters the cell partly by diusion and is converted to its active form through aquation reactions replacing its chloride ions with water or hydroxyl groups. e mono-aquated active metabolite reacts with cellular DNA to form interstrand and intrastrand cross-links. ese distort DNA structure and block nucleotide replication and transcription leading to DNA breaks and miscoding (Figure 6.2). ese damages may be repaired but, if not repaired, will be mutagenic or lethal. In the last case, the lesion activates an irreversible sequence of events culminating in apoptosis. e formation of the active species is, however, subject to
inactivation by endogenous nucleophiles such as glutathione, methionine, and metallothionein.
