Electrophoretic analysis of DNA modifications induced by cis- and trans-diamminedichloroplatinum (II) during heat-denaturation of conformation isomers of pBR322 DNA.
The use of conformation isomers of pBR322 DNA in the study of interactions of Pt complexes with DNA provided for a good monitoring of induced changes in the structure of DNA by gel electrophoresis. On the basis of characteristic changes in the gel electrophoretic mobility of platinated isomers of pBR322 DNA we detected the presence of Pt-DNA adducts representing both intra- and interstrand bifunctional binding of Pt complexes to DNA. Also, this method made it possible to distinguish between DNA modifications induced by the therapeutically active cis-diamminedichloroplatinum (II) (cis-DDP) alone, and those induced by its therapeutically inactive trans-isomer (trans-DDP). The electrophoretically detected DNA modifications were more effective if the interaction of the Pt complex took place with heat-denatured DNA. This process, as compared to that performed with native DNA, ran 100 times faster.
Rauko
P
P
Cancer Research Institute, Bratislava, Czechoslovakia.
Hrubisko
M
M
Hanusovská
E
E
D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004586:Electrophoresis; D005557:Formaldehyde / Q000494:pharmacology; D006358:Hot Temperature; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013237:Stereoisomerism; D014158:Transcription, Genetic
D005557:Formaldehyde; D004247:DNA; D002945:Cisplatin