Molecular mechanism of cell death induced dNTP pool imbalance.

We have previously reported that treatment of the FM3A cells with 5-fluorodeoxyuridine (FdUrd) induced DNA double strand breaks and cell death. We proposed the hypothesis of dNTP pool imbalance death in order to understand these phenomena: intracellular dNTP pool imbalance induced by FdUrd would be a trigger for activation or induction of endonuclease which would attack DNA to cause double strand breaks and subsequent cell death. To observe the mechanism of dNTP imbalance death we have purified and characterized the endonuclease that was detected in FdUrd treated FM3A cells but not untreated cells. As the result, we suggested that purified enzyme is a new endonuclease and responsible for DNA degradation component of the apoptotic process. Furthermore, we study that mRNA levels of nuclear protooncogenes, c-fos, c-jun and c-myc, in FdUrd-treated cells. These results suggested that the endonuclease might be induced by the protooncogene related pathway and generates DNA fragments accompanied by cell death.