THE CYTOTOXIC ACTION OF 4 AMMINE AMINE PLATINUM(IV) DICARBOXYLATES - A FLOW CYTOMETRIC STUDY/

We have used Bow cytometry to study the mechanism of cytotoxic action of a series of ammine/amine Pt(IV) dicarboxylates [ammine diacetatodic hloro(cyclohexylamine) platinum(IV), JM216; ammine dibutyratodichloro( cyclohexylamine)platinum(IV) JM221; ammine diacetatodichloro(propylami ne)platinum(IV), JM223; ammine dibenzoalodichloro(propylamine)platinum (IV), JM244]. JM216 has been shown to have clinical potential and has recently entered phase II trials. All the compounds caused a slowdown in S-phase transit followed by a block in G(2). Cells died either thro ugh apoptosis (largely during S-phase) or by Failing to overcome the G (2) block (some days after treatment). In G(2), the cells either divid ed or enlarged and died. Al equitoxic doses, JM216 showed the most apo ptotic cells and had the most platinum bound ro the DNA; JM244 showed the fewest apoptotic cells and had the least platinum bound to DNA. We suggest that whether apoptosis was triggered or not was governed by t he total amount of Pt bound to the DNA; the type of lesion was more im portant in determining whether a cell became blocked in G(2).