Comparative study between the interaction of dephosphorylated amifostine (WR-1065) and amoxicilline with pBR322 in absence and presence of cisplatin by AFM.
The effect of the amoxicilline as a possible cisplatin-action protector on pBR322 DNA has been visually studied by atomic force microscopy in comparison with the modifications caused by the controversed cisplatin protector amifostine. Incubation of amoxicilline with the plasmid DNA showed aggregation and compaction of DNA. Cisplatin incubated in the same conditions with DNA produced kinks and super-coiling of the circular form. In the case of previous treatment of DNA with amoxicilline, the characteristic effect of cisplatin is only partially observed. The amoxicilline seemed to control the action of cisplatin on DNA. The initial effect of dephosphorylated amifostine (WR-1065) when this protector was incubated with the plasmid was also the formation of aggregates and the compaction of DNA. However, addition of cisplatin successively after 1 and 2 h showed the characteristic modification caused by cisplatin but only in a decreasing percentage of molecules of DNA. Both molecules, amoxicilline and WR-1065 seem to control the strong direct action of cisplatin on DNA. This effect can justify the role as protecting agent of amifostine on side effects caused by cisplatin and can open new possibilities to other agents like amoxicilline.
Amat
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Departament de Físicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Diagonal 643, 08028 Barcelona, Spain.
Prieto
M J
MJ
Moreno
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V
D004999:Amifostine / Q000737:chemistry; D000658:Amoxicillin / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D008624:Mercaptoethylamines / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D010957:Plasmids; D012997:Solvents
D000970:Antineoplastic Agents; D008624:Mercaptoethylamines; D012997:Solvents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D000658:Amoxicillin; D004247:DNA; D004999:Amifostine; D002945:Cisplatin