Action of Platinum—Amine Complexes

A true sensitizing action for platinum complexes is likely to require a reduction to Pt(I). The rate constants for reaction of c/5-[PtCl2(NH3)2] with e and OH have been calculated as 1.8 X 10 and 2.0 X 10  

Reoxidation will involve Pt(II) aqua and hydroxo complexes because of 

These points also explain the semantic differences between a modifier or potentiator of radiation damage (by whatever mechanism) and a sensitizer (implying oxygen-mimetic or electron-accepting mechanisms) although the literature is not always consistent on this point. The radiation potentiation of platinum amine complexes in vitro is remarkably, and somewhat frustratingly, dependent on experimental conditions such as the time of incubation before irradiation and the phase of the cell cycle used occasional protection has even been seen by most workers. Consideration of these factors requires careful analysis of the shape and slope of the survival curves and is beyond the scope of this summary, but the factors need to be known for a complete description of the potentiating effect. 

Radiation-induced thymine release from DNA is also inhibited by cisplatin [78]. The possibility exists that platination of DNA (presumably via the purine bases at biologically relevant concentrations) may affect the inherent radiosensitivity of the bases, which for aerated solutions, follows the order Thy Cyt Ade Gua. An analysis of this type of damage should take into consideration profiles of base release and decomposition with and without platination, as well as the effects the conformational and electronic changes in platinated DNA will have on the radiation interaction. In this respect the studies on radiosensitivity of Ag and Hg DNA complexes [85], as well as the effects on the radiation chemistry of simple bases of Cu(II) [86] and Fe(III) [87], are relevant. 

Attempts have been made to separate out the components of damage caused by platinum complexes [52, 84]. The extra burden placed on 

---