Cytotoxicity and mutagenicity of trans,trans,trans-[PtCl2(CH3COO)2(NH3)(1-adamantylamine)] [trans-adamplatin(IV)] and its reduced analog trans-[PtCl2(NH3)(1-adamantylamine)] [trans-adamplatin(II)] were examined. In addition, the several factors underlying biological effects of these trans-platinum compounds using various biochemical methods were investigated. A notable feature of the growth inhibition studies was the remarkable circumvention of both acquired and intrinsic cisplatin resistance by the two lipophilic trans-compounds. Interestingly, trans-adamplatin(IV) was considerably less mutagenic than cisplatin. Consistent with the lipophilic character of trans-adamplatin complexes, their total accumulation in A2780 cells was considerably greater than that of cisplatin. The results also demonstrate that trans-adamplatin(II) exhibits DNA binding mode markedly different from that of ineffective transplatin. In addition, the reduced deactivation of trans-adamplatin(II) by glutathione seems to be an important determinant of the cytotoxic effects of the complexes tested in the present work. The factors associated with cytotoxic and mutagenic effects of trans-adamplatin complexes in tumor cell lines examined in the present work are likely to play a significant role in the overall antitumor activity of these complexes.
- MeSH
- adukty DNA chemie MeSH
- amantadin analogy a deriváty farmakologie chemie metabolismus MeSH
- antitumorózní látky farmakologie chemie metabolismus MeSH
- cirkulární dichroismus MeSH
- DNA chemie MeSH
- financování organizované MeSH
- hypoxanthinfosforibosyltransferasa genetika účinky léků MeSH
- lidé MeSH
- mutageny farmakologie chemie metabolismus MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny chemie metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
