Some of six-coordinate PtIV complexes show anticancer activity, especially to tumors which are resistant to cisplatin. It is generally believed that since PtIV compounds are inert in ligand substitution reactions relative to their PtII analogs, they must be reduced to PtII species before binding to DNA. However, there are numerous experimental results which cannot be entirely explained by this presumption. Some PtII analogs do not show any of the potency or selectivity of their PtIV counterparts. These experimental results suggest that not every PtIV complex behaves the same way in its reactivity. Depending on the nature of the ligands and reaction conditions, some PtIV complexes may undergo a reasonably fast substitution reaction via autocatalysis. Sometimes DNA itself may be involved in the reduction of PtIV complexes, resulting in different final DNA structure which is more difficult to repair than the PtII modified DNA. In this research, the anticancer activity of a Pt(IV) complex, 1,2-diaminocyclohexanetetrachloroplatinum(IV) (PtIV(dach)Cl4, tetraplatin), and its reactivity with DNA are compared with its PtII analog, PtII(dach)Cl2. PtIV(dach)Cl4 shows much higher cytotoxicity than PtII(dach)Cl2 on both L1210/0 and L1210/10 cells. The reaction mixtures of PtIV(dach)Cl4 with monomeric and oligomeric DNA contain 8-oxoguanine inicating PtIV(dach)Cl4 oxidizes guanine in DNA, which is not the case for PtII(dach)Cl2. These results strongly suggest that this oxidative damage differentiate the anticancer activity of PtIV complexes from their PtII analogs. PtIV anticancer drugs are not just PtII pro-drugs; they can oxidize DNA, which PtII cannot do.