Topology effect for DNA structure of cisplatin: topological transformation of cisplatin-closed circular DNA adducts by DNA topoisomerase I.
The reaction of cis-Pt(NH3)2Cl2(cis-DDP)-closed circular DNA adducts with DNA topoisomerse I(topo I) were studied by electron microscopy. We identified unique topoisomers such as a singly-linked catenane (2(1)2), trefoil (3(1), and dimetric catenane (2(1)2), etc., by analysis with electron micrographs. These unique recombination products resulted from cis-DDP-intra-twisting looped DNA adducts by DNA topo I, and the products could be explained a new mechanism based on an odd-even number rule. Our results suggest a new model on the working mechanisms for DNA topology of cis-DDP which enhances the recombination of DNA. Based on our results, we propose the topological idea that the yields of a mini closed circular DNA and pseudo trefoil DNA, etc., can be expected by reaction of cis-DDP-DNA-histone complexes with DNA topo I in the body.
Department of Drug Analysis, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
S
S
Kobayashi
M
M
Furukawa
C
C
Dohi
H
H
Hamashima
T
T
Arai
A
A
Tanaka
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology*; D018736:DNA Adducts / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000378:metabolism; D004270:DNA, Circular / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D004587:Electrophoresis, Agar Gel; D007536:Isomerism; D008854:Microscopy, Electron; D009690:Nucleic Acid Conformation; D011995:Recombination, Genetic / Q000187:drug effects
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004270:DNA, Circular; D004264:DNA Topoisomerases, Type I; D002945:Cisplatin