Effect of Heavy Metals on the In Vitro Cytotoxicity of 3-Ethoxy-2-Oxobutyraldehyde Bis(Thiosemicarbazone) and Related Compounds
- 1 July 1973
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 51 (1) , 139-146
- https://doi.org/10.1093/jnci/51.1.139
Abstract
We studied the effect of trace metals on the in vitro cytotoxicity of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) (H2KTS) and several related thiosemicarbazones, using a modification of the Arai-Suzuki test system in which metal ion concentrations are rigidly controlled. In the absence of trace metal ions, none of the compounds was cytotoxic, but several became highly cytotoxic in the presence of nontoxic levels of Cu2+ or Zn2+. The ability of either cupric or zinc ion to potentiate the activity of derivatives of 3-ethoxy-2-oxobutyraldehyde and pyruvaldehyde depended on whether the thlcsemlccrbczene groups were methylated at the N4 position. Among several metal chelates of H2KTS, only the cupric, cuprous, and mercuric chelates had appreciable effects and these were increased by the presence of cupric ion. The in vitro cytotoxicity of H2KTS to Walker 256 tumor cells in the presence of cupric ions correlates with the inability of similarly treated tumor cells to grow when implanted into rats. The cytotoxic form of each active compound appears to be the chelate of the metal activating that compound.Keywords
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