Wataya Y, Hwang H, Nakazawa T, Takahashi K, Otani M, Igaki T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Nucleic Acids Symp Ser. 1993(29):109-10.
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.
我们之前曾报道，用5-氟脱氧尿苷（FdUrd）处理FM3A细胞会诱导DNA双链断裂并导致细胞死亡。为了解这些现象，我们提出了dNTP库失衡死亡的假说：FdUrd诱导的细胞内dNTP库失衡会触发核酸内切酶的激活或诱导，该酶会攻击DNA导致双链断裂并随后引起细胞死亡。为了观察dNTP失衡死亡的机制，我们纯化并鉴定了在经FdUrd处理的FM3A细胞中检测到但未经处理的细胞中未检测到的核酸内切酶。结果，我们认为纯化的酶是一种新的核酸内切酶，并且是凋亡过程中DNA降解成分的原因。此外，我们研究了FdUrd处理的细胞中核原癌基因c-fos、c-jun和c-myc的mRNA水平。这些结果表明，核酸内切酶可能由原癌基因相关途径诱导，并伴随着细胞死亡产生DNA片段。
