Influence of cisplatin on DNA and RNA stability

Abstract: Cancer is today a common disease in our society. There are several forms of cancer and some can be treated with cytostatic drogs. The most common form of cancer among men in the age of 20-35 is testicular cancer. Testicular cancer can be treatedwith cisplatin or oxaliplatin. The therapeutic use of cisplatin was discovered in the late 60's by Barnett Rosenberg. The main target of cisplatin is to bind DNA and prevent the cell from dividing. In order for cisplatin to work, it has to be activated. Cisplatin in the bloodstream is stable due to the high concentration of chloride ions, but when it enters the cell, the chloride ion concentration is lower the chloride ligands are exchanged for two water ligands. This makes it possible for cisplatin to bind to DNA. Upon temperature increase the two strands in double stranded DNA will separate into single strands. The definition of the thermal melting point is when half of the DNA is double stranded and half of the DNA is single stranded. The thermal melting point of the DNA decreases when cisplatin binds to it. This is due to the altered structure of the DNA. In this study, the difference was measured to be 10 °C. The thermal melting point measurement showed that RNA had a higher value than DNA. Though there was no difference between the platinated and unplatinated RNA. The oligonucleotide was enzymatically digested, to be able to study were cisplatin was bound to the DNA. The components were separated by chromatography. A reverse phase C18 column was used. The polar bases will elute earlier than the more non-polar bases.