Species differences in the induction of hepatocellular DNA synthesis by diethanolamine.
Species differences in the induction of hepatocellular DNA synthesis by diethanolamine.
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二乙醇胺诱导肝细胞 DNA 合成的物种差异。
DOI：
10.1093/toxsci/kfi252
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Klaunig,JamesE
中科院分区：
文献类型：
--
作者：
Kamendulis,LisaM;Klaunig,JamesE
二乙醇胺增加了慢性接触后小鼠肝脏肿瘤的发生率和多样性。已知二乙醇胺抑制细胞胆碱摄取。由于胆碱缺乏在啮齿动物中产生肿瘤，二乙醇胺，通过胆碱消耗，可能导致啮齿动物中的肿瘤发展。尚不清楚二乙醇胺通过这种作用模式在人体中发挥作用的潜力。本研究检查了二乙醇胺（0-500 μg/ml）和胆碱耗竭对小鼠、大鼠和人肝细胞原代培养物中DNA合成和细胞生长途径相关基因表达变化的影响。在小鼠和大鼠肝细胞中，用10 μg/ml或更高浓度的二乙醇胺处理后，DNA合成增加（是对照的3- 4倍）。相比之下，二乙醇胺未能增加人肝细胞中的DNA合成。在含还原胆碱的培养基（正常培养基的1/10至1/100; 0.898至0.0898 mg/l vs. 8.98 mg/l）中孵育肝细胞可增加DNA合成（小鼠和大鼠肝细胞中分别为对照的1.6倍和1.8倍）;然而，胆碱耗竭不会诱导人肝细胞中的DNA合成。小鼠和大鼠肝细胞培养在培养基中补充2- 50倍过量胆碱减少二乙醇胺诱导的DNA合成控制水平或以下。二乙醇胺处理后小鼠和大鼠肝细胞的基因表达分析显示，与细胞生长相关的基因增加，参与凋亡途径的基因表达减少。这些结果支持胆碱耗竭是二乙醇胺诱导啮齿动物肝肿瘤作用模式的核心的假设。此外，由于二乙醇胺处理或胆碱耗竭未能诱导人肝细胞中的DNA合成，因此这些结果表明，人类可能没有二乙醇胺致癌作用的风险。
Diethanolamine increased the incidence and multiplicity of liver tumors in the mouse following chronic exposure. Diethanolamine is known to inhibit cellular choline uptake. Since choline deficiency produces tumors in rodents, diethanolamine, through choline depletion, may result in tumor development in rodents. The potential for diethanolamine to function through this mode of action in humans is not known. The present studies examined the effect of diethanolamine (0–500 μg/ml) and choline depletion on DNA synthesis and changes in expression of genes involved in cell growth pathways in primary cultures of mouse, rat, and human hepatocytes. In mouse and rat hepatocytes DNA synthesis was increased following treatment with 10 μg/ml diethanolamine and higher (3- to 4-fold over control). In contrast, diethanolamine failed to increase DNA synthesis in human hepatocytes. Incubation of hepatocytes in medium containing reduced choline (1/10 to 1/100 of normal medium; 0.898 to 0.0898 mg/l vs. 8.98 mg/l) increased DNA synthesis (1.6- and 1.8-fold of control in mouse and rat hepatocytes, respectively); however, choline depletion did not induce DNA synthesis in human hepatocytes. Mouse and rat hepatocytes incubated in medium supplemented with 2- to 50-fold excess choline reduced diethanolamine-induced DNA synthesis to control levels or below. Gene expression analysis of mouse and rat hepatocytes following diethanolamine treatment showed increases in genes associated with cell growth and decreases in expression of genes involved in apoptotic pathways. These results support the hypothesis that choline depletion is central to the mode of action for the induction of rodent hepatic neoplasia by diethanolamine. Furthermore, since diethanolamine treatment or choline depletion failed to induce DNA synthesis in human hepatocytes, these results suggest that humans may not be at risk from the carcinogenic effects of diethanolamine.
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DOI：
10.1016/s0021-9258(17)40293-6
发表时间：
1977
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Fenton;M. Fasco;A. B. Stackrow
通讯作者：
A. B. Stackrow
牛因子 V 和因子 V 衍生肽与磷脂囊泡的相互作用。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Higgins,DL;Mann,KG
通讯作者：
Mann,KG
单链牛因子 V 的分离和表征。
影响因子：
4.8
作者：
M. Nesheim;K. Myrmel;L. Hibbard;K. Mann
通讯作者：
K. Mann
人凝血因子 V 的纯化和表征。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kane,WH;Majerus,PW
通讯作者：
Majerus,PW
人血小板因子V的分离。
影响因子：
20.3
作者：
Viskup,RW;Tracy,PB;Mann,KG
通讯作者：
Mann,KG