Proliferation-dependent cytotoxicity of diethylenetriaminepentaacetate (DTPA) in vitro

The effect of Ca-DTPA in the dose range from 0.1 to 10 mM on proliferating Chinese hamster lung cells was studied by flow-microfluorometry. Whereas 0.1 mM Ca-DTPA leads to a partial and reversible block in G1 only, higher concentrations bring about a marked G1-block followed by cell death in the S-phase. Zn-DTPA was without any effect and the cytotoxicity of Ca-DTPA is, consequently, ascribed to its interference with the metal requirement of the synthesis of proteins and DNA. In the case of cells under non-proliferating conditions higher doses of Ca-DTPA (>= 10 mM) are needed to kill the cells; this holds also for Zn-DTPA (>60 mM). It is tentatively suggested that the toxic action of both chelates in this case is due to a damage of the cell membrane as a consequence of the removal of Ca2+ by the formation of bimetallic chelates. (author)