Cisplatin induces loop structures and condensation of single DNA molecules.
Structural properties of single lambda DNA treated with anti-cancer drug cisplatin were studied with magnetic tweezers and AFM. Under the effect of low-concentration cisplatin, the DNA became more flexible, with the persistence length decreased significantly from approximately 52 to 15 nm. At a high drug concentration, a DNA condensation phenomenon was observed. Based on experimental results from both single-molecule and AFM studies, we propose a model to explain this kind of DNA condensation by cisplatin: first, di-adducts induce local distortions of DNA. Next, micro-loops of approximately 20 nm appear through distant crosslinks. Then, large aggregates are formed through further crosslinks. Finally, DNA is condensed into a compact globule. Experiments with Pt(dach)Cl(2) indicate that oxaliplatin may modify the DNA structures in the same way as cisplatin. The observed loop structure formation of DNA may be an important feature of the effect of platinum anti-cancer drugs that are analogous to cisplatin in structure.
Hou
Xi-Miao
XM
Laboratory of Soft Matter Physics, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
Zhang
Xing-Hua
XH
Wei
Kong-Ji
KJ
Ji
Chao
C
Dou
Shuo-Xing
SX
Wang
Wei-Chi
WC
Li
Ming
M
Wang
Peng-Ye
PY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D010582:Bacteriophage lambda / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure*; D004279:DNA, Viral / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D004548:Elasticity; D018625:Microscopy, Atomic Force; D009690:Nucleic Acid Conformation; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D004279:DNA, Viral; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D004247:DNA; D002945:Cisplatin