Interaction of DNA and purine nucleosides with cis-dichlorodiammineplatinum(II) and antimitotic activity of the complexes on meristematic root cells.
The appropriate experimental conditions for the preparation of complexes of cis-dichlorodiammineplatinum(II) with DNA and with purine nucleosides have been determined which leave negligible amounts of free drug in the solution. Important conformational changes of DNA upon binding to cis-Pt(NH3)2-Cl2 have been evidenced through viscosity, electric birefringence and thermal denaturation experiments. The antimitotic and antitumor activity of the drug was found to be totally inhibited by its binding to DNA and to the purine nucleosides. Enzymic degradation observations on the DNA-cis-Pt(NH3)2Cl2 complexes indicated an important inhibition of the degradation and the absence of release of free drug. The implications of the results in relation with the mode of binding of this compound to DNA, with the choice of carriers for drugs and the mechanism of action of lysosomotropic agents are discussed.
D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D009691:Nucleic Acid Denaturation; D059828:Plant Cells; D011684:Purine Nucleosides / Q000378:metabolism / Q000494:pharmacology*
D011684:Purine Nucleosides; D004247:DNA; D002945:Cisplatin