Cisplatin intra strand

In primary rahhit proximal tuhular (RPT) cells cisplatin exposure resulted in an inhihition of DNA synthesis, which is most likely related to the primary anti-tumorigenic mechanism of this compound i.e. DNA inter and intra strand cross linking [117]. RNA and protein synthesis were decreased in RPT cells and quiescent LLC-PK cells upon cisplatin exposure [117, 118]. Other effects of cisplatin on cultured RPT include a decrease in glucose uptake, an inhihition of Na -K ATPase and alterations in total glutathione content [117]. In the normal rat kidney (NRK) cell hne cisplatin (IpM for 48h) induced a marked increase in the level of lipid peroxides [119]. 

Cisplatin (dx-Diamminedichloroplatinum) is a divalent water-soluble platinum containing complex. It reacts directly with DNA, resulting in both intra-and inter-strand cross-links. It also causes DNA breaks and it inhibits DNA replication and RNA transcription. A mechanism for the occurrence of resistance appears to be an increased of the levels of DNA-excision repair enzymes. Cisplatin is used in combination therapies with other anticancer drugs in the treatment of testicular and ovarian cancers and it has also shown high activity against cancers of the bladder, head, neck and endometrium. It is administered intravenously by rapid injection or by continuous infusion. It is for more that 90% bound to... 

Various modes of coordination of the platinum(II) drug cisplatin to bases in DNA strands, following initial chloride hydrolysis a guanine N-donor (G) is favoured. Actual models determined from structural studies of intra- (at left) and inter-strand (at right) coordination to DNA oligomers (drawn from the Protein Data Bank DOI 10.2210/pdblddp/pdb and 10.2210/pdblksb/pdb) are also shown. 

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