Differences in the consequences of the decay of radioactive 64Cu atoms incorporated in cells under either in vitro or in vivo conditions.

To study the lethal effect of 64Cu under in vitro conditions, asynchronous mammalian cells were used. A lethal effect does exist as a consequence of the decay itself of a few 64Cu atoms incorporated in cellular DNA. This lethal effect is characterized by an exponential survival curve with no shoulder and no tail; it exists even for non-dividing cells. The lethal efficiency per decay is very high. To test the 64Cu lethal effect under in vivo conditions, experiments were performed with ascitic cells developing in mice. In this case, the lethal effect also exists, but it is not a function of the 64Cu doses injected in the mice. Faced with this puzzling result, a systemic approach was necessary to understand and counteract ascitic cells developing in mice.