Imbalance of deoxyribonucleoside triphosphates and DNA double-strand breaks in mouse mammary tumor FM3A cells treated in vitro with an antineoplastic tropolone derivative.
Imbalance of deoxyribonucleoside triphosphates and DNA double-strand breaks in mouse mammary tumor FM3A cells treated in vitro with an antineoplastic tropolone derivative.
复制标题
DOI：
10.1111/j.1349-7006.1992.tb00141.x
复制
发表时间：
1992-06
期刊：
影响因子：
--
通讯作者：
Wataya Y
中科院分区：
文献类型：
--
作者：
Yamato M;Hirota Y;Yoshida S;Tanaka S;Morita T;Sakai J;Hashigaki K;Hayatsu H;Wataya Y
研究了 α,α-双(2-羟基-6-异丙基托彭-3-基)-4-甲氧基甲苯 (JCI-3661) 杀死小鼠乳腺肿瘤 FM3A (F28-7) 细胞的机制。当细胞暴露于 3.7 μM 的药物时，由于 dGTP 和 dATP 减少以及 dTTP 增加，细胞内 dNTP 池变得不平衡。 dNTP 失衡的模式与羟基脲引起的相同。当 JCI-3661 添加到培养基中时，成熟的 DNA 链断裂，产生 100-200 KB 对的片段（通过正交场交替凝胶电泳发现）。添加后 12 小时，在细胞中观察到通过该技术检测到的 DNA 链断裂。在培养后约 14 小时（台盼蓝染色）或约 12 小时（集落形成能力）观察到细胞死亡的开始。通过碱性和中性过滤洗脱测定法测量，DNA 单链和双链的断裂在用 3.7 μM JCI-3661 处理 24 小时后变得明显。将 JCI-3661 引起的单链和双链断裂比率与辐射后的比率进行比较表明，JCI-3661 仅断裂双链。放线菌酮可抑制 JCI-3661 引起的双链断裂和细胞死亡。 JCI-3661 对 DNA 合成的抑制作用大于对 RNA 或蛋白质合成的抑制作用。 DNA 双链断裂可能在 JCI-3661 引起的细胞死亡中发挥重要作用。
The mechanism by which α,α‐bis(2‐hydroxy‐6‐isopropyltropon‐3‐yl)‐4‐methoxytoluene (JCI‐3661) kills mouse mammary tumor FM3A (F28–7) cells was studied. When the cells were exposed to the drug at 3.7 μM, the intracellular dNTP pool became unbalanced because of decreases in dGTP and dATP and an increase in dTTP. The pattern of the dNTP imbalance was the same as that caused by hydroxyurea. When JCI‐3661 was added to the culture medium, mature DNA strands broke, giving fragments of 100–200 kilobase pairs long as found by orthogonal‐field‐alternation gel electrophoresis. DNA strand breaks, detected by this technique, were observed in the cells at 12 h after the addition. The beginning of cell death was observed at about 14 h (trypan blue staining) or at about 12 h (colony‐forming ability) after cultivation Breaks in the single and double strands of DNA, as measured by alkaline and neutral filter elution assay, became evident 24 h after treatment with 3.7 μM JCI‐3661. Comparison of the ratio of single‐ and double‐strand breaks caused by JCI‐3661 to that following radiation suggested that JCI‐3661 broke only double strands. Cycloheximide inhibited both the breakage of double strands and the cell death caused by JCI‐3661. JCI‐3661 decreased DNA synthesis more than RNA or protein synthesis. The breaks in double strands of DNA were probably important in the cell death caused by JCI‐3661.
登录
查看更多内容
DOI：
10.1073/pnas.79.7.2211
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
TOPAL, MD;BAKER, MS
通讯作者：
BAKER, MS
影响因子：
2.9
作者：
TANAKA, K;YOSHIOKA, A;WATAYA, Y
通讯作者：
WATAYA, Y
DOI：
10.1016/0005-2787(66)90043-8
发表时间：
1966-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
COLOMBO, B;FELICETTI, L;BAGLIONI, C
通讯作者：
BAGLIONI, C
影响因子：
14.9
作者：
BRADLEY, MO;KOHN, KW
通讯作者：
KOHN, KW
影响因子：
3.3
作者：
BONURA, T;SMITH, KC
通讯作者：
SMITH, KC