Chemotherapeutic DNA-damaging agents. Chemotherapeutic agents act by preferentially damaging the DNA of fast-dividing tumor cells. (a) Cisplatin is a cross-linking reagent that reacts with N-7 of two G residues to form intrastrand or interstrand cross-links. (b) Bleomycin binds to DNA and forms reactive oxygen species (not shown) that cause strand breaks. Iron normally binds bleomycin, but cobalt was used to prevent DNA modification in the crystal structure shown here. (c) Doxorubicin is a DNA intercalator, inserting between adjacent nucleotide residues. Intercalators can cause frameshift mutations during replication, or they can block replication forks, making the forks susceptible to nucleases that cause strand breaks.