Preferential interstrand cross-linking of DNA rich in guanine and cytosine by cis-dichlorodiammineplatinum(II).
Two native DNAs differing in G + C content were bound equally with the antitumour drug cis-Pt(NH3)2Cl2 at increasing Pt/P ratios. Resulting changes in their ultraviolet absorption spectra show equal fractional decreases in the initially different values of A250/A270 for the two DNAs, and less prominent bathochromic and hyperchromic shifts for DNA richer in G + C. Changes in the absorbance (A260) observed before and after subjecting the DNA samples to the conditions of denaturation (with alkali) and renaturation, indicate the following effects of the platinum binding. Maximum renaturation occurs at 50% lower Pt/P ratio of 0.03 for Micrococcus lysodeikticus DNA (72% G + C) than 0.06 for salmon sperm DNA (41% G + C) and is maintained at higher Pt/P ratios. Interstrand cross-links that facilitate renaturation, cause an incomplete melting of DNA so that the platinum-DNA complex at pH 12.5 has a reduced absorbance. This effect is more evident for the platinum complex with DNA richer in G + C due to more interstrand cross-links. Platinum-induced destabilisation of DNA, shown by its hyperchromicity at the pre-melting state (pH 6--7, 25 degrees C) and also by a lowering of the pH corresponding to the mid-point of its melting, is less evident for DNA richer in G + C.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin; D003432:Cross-Linking Reagents; D003596:Cytosine; D004247:DNA; D004269:DNA, Bacterial; D006147:Guanine; D007700:Kinetics; D008297:Male; D008837:Micrococcus; D012474:Salmon; D013056:Spectrophotometry, Ultraviolet; D013094:Spermatozoa
D003432:Cross-Linking Reagents; D004269:DNA, Bacterial; D006147:Guanine; D003596:Cytosine; D004247:DNA; D002945:Cisplatin