The Mechanism of Action of Antilturnour Platinum Compounds

As a result of observations madc by Roscnberg in the early 1960s~ a range of platinum compounds have been discovered which have significant anti-tumour properties (I, 2). The two prototype compounds originally mvcstigated are the cis isomers of diamminoplatinum(I1) dichloride and diammino-platinum(1V) tetrachloride. The stercochemistries are shown in Figure I . The t ~ m s i omers of these complexes are ineffective as ailti-tumour agents. The cis-diammino-platinum(I1) dichloride has now had an extensive clinical trial as an anti-tumour drug (3). The cis isomers are highly effective cell poisons which inhibit the replication of rapidly dividir?g cells. There is no evidence that the compounds so far examined are selective for tumour cells; indeed, many classes of rapidly growing cells are damaged by these agents. The effectiveness of killing cells depends upon the dose of drug received but not in a linear way. It has been demonstrated that at low doses some types of cell have a mechanism for recovery from the damage inflicted by the drug. In these respects the platinum compounds are not dissimilar from other anti-tumour agents such as alkylating agents or X-irradiation. In addition to their anti-tumour properties the cis platinum compounds display a variety of other biological effects which are significant to our understanding of their mechanism of action. For example, they induce bacterial The exact nature of this