Biological Effects Implying DNA as Target

The biological effects of cisplatin implicating DNA as the primary target in vivo have been summarized [69—73,29]. Briefly, these include  

To these biological effects a number of biochemical effects also are shown to be DNA-related  

The overall biological effects indicative of interference with replication could, of course, have direct or indirect causes. The summarized biochemical effects argue for a direct effect. For more details see the references quoted above. A recent provocative study argues against quantitative correlations between antitumour activity and inhibition of DNA synthesis [73]. Certainly, other platinum complexes can inhibit DNA synthesis but do not produce antitumour effects (see Chapter 3). This difference, one of the great fascinations of the field, has focused attention on the nature of the binding (lesions) of the a isomer to DNA, in order to explain this unique specificity. 

In this latter respect the overall role of repair processes is receiving increasing attention [29, 71]. The physical binding of any drug to DNA is eventually translated into cell death by an inability to replicate, which also results from an inabihty of the cell to repair that lesion. The nature of that specific lesion for cisplatin and the explanation of why tumour cells are less capable of its repair (since the complex must be somewhat selectively toxic to tumour cells) lie, then, at the heart of the understanding of the mechanism of action. 

---