Plasmodium falciparum: DNA sequence specificity of cisplatin and cisplatin analogues

In this paper, we provided evidence that cisplatin is able to form adducts with cellular DNA in Plasmodium falciparum. The DNA sequence specificity of cisplatin adduct formation was determined in trophozoite-enriched P. falciparum cells and this paper represents the first occasion that the sequence specificity of cisplatin DNA damage has been observed in malaria cells. Utilising a sub-telomeric, 692 bp repeat sequence in the P. falciparum genome, we were able to investigate the DNA adducts formed by cisplatin and five analogues. A run of eight consecutive guanines was the most prominent site of DNA damage in the malarial cells. This study suggests that the mechanism of P. falciparum cell death caused by cisplatin involves damage to DNA and hence inhibition of DNA replication and cell division. (C) 2011 Elsevier Inc. All rights reserved.