Otani M, Yoshida S, Yoshioka-Hiramoto A, Nakazawa T, Wataya Y
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Nucleic Acids Symp Ser. 1991(25):111-2.
The mechanism of intracellular deoxyribonucleoside-triphosphates (dNTP) pool imbalance-induced cell death in mouse FM3A (F28-7) cells was studied. When the cells were treated with 5-fluorodeoxyuridine (FdUrd), deoxyadenosine, 2-chlorodeoxyadenosine, or alpha,alpha-bis(2-hydroxy-6-isopropyltropon-3-yl)-4-methoxytolu ene, an imbalance in the cellular dNTP pool was induced. The imbalance was followed by DNA double-strand breaks and subsequent cell death. Fragmented DNA appeared to be approximately 100-200 kbp in size. The base of 5'-termini in the DNA were adenine and thymine. The endonuclease toward double stranded DNA has been found in a fraction of FdUrd treated cell lysate, and isolated using column chromatography. We propose the new mechanism dNTP pool imbalance induced cell death named; dNTP Imbalance Death.
研究了小鼠FM3A（F28-7）细胞中细胞内脱氧核糖核苷三磷酸（dNTP）库失衡诱导细胞死亡的机制。当用5-氟脱氧尿苷（FdUrd）、脱氧腺苷、2-氯脱氧腺苷或α，α-双（2-羟基-6-异丙基肌钙蛋白-3-基）-4-甲氧基甲苯处理细胞时，会诱导细胞dNTP库失衡。这种失衡随后会导致DNA双链断裂并引发细胞死亡。断裂的DNA大小似乎约为100-200kbp。DNA 5'-末端的碱基是腺嘌呤和胸腺嘧啶。在一部分FdUrd处理的细胞裂解物中发现了针对双链DNA的核酸内切酶，并通过柱色谱法进行了分离。我们提出了一种新的dNTP库失衡诱导细胞死亡的机制，称为dNTP失衡死亡。
