Effect of rodent hepatocarcinogenic peroxisome proliferators on fatty acyl-CoA oxidase, DNA synthesis, and apoptosis in cultured human and rat hepatocytes.
Effect of rodent hepatocarcinogenic peroxisome proliferators on fatty acyl-CoA oxidase, DNA synthesis, and apoptosis in cultured human and rat hepatocytes.
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啮齿动物肝癌过氧化物酶体增殖剂对培养的人和大鼠肝细胞中脂肪酰辅酶A氧化酶、DNA合成和细胞凋亡的影响。
DOI：
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发表时间：
1998
影响因子：
3.8
通讯作者：
Gary M. Williams
中科院分区：
文献类型：
--
作者：
C. Perrone;Lihua Shao;Gary M. Williams
在培养的大鼠和人肝细胞中比较了啮齿动物肝癌物质氯贝酸和二丙贝特对过氧化物酶体脂肪酰基辅酶A氧化酶活性、DNA合成和细胞凋亡的影响。与人类肝细胞相比，大鼠肝细胞表达的过氧化物酶体脂肪酰基辅酶A氧化酶水平高出10倍。在最高浓度（1.0 mM）下，两种药物均诱导大鼠和人肝细胞中该酶的活性增加两到三倍。环丙贝特（0.1 和 0.2 mM）使大鼠肝细胞中的 DNA 合成增加两倍，而氯贝酸对这些细胞中的 DNA 合成没有影响。相比之下，氯贝酸和环丙贝特浓度的增加都会抑制人肝细胞中的 DNA 合成。通过末端转移酶dUTP-生物素缺口末端标记技术，观察到0.1和0.2 mM氯贝酸和环丙贝特可抑制转化生长因子-β（TGFβ）诱导的大鼠肝细胞凋亡50%，但对TGFβ诱导的人肝细胞凋亡没有影响。尽管氯贝酸和环丙贝特减少了TGFβ诱导的细胞凋亡，但它们对大鼠肝细胞培养物中的基础细胞凋亡水平没有影响。然而，这两种药物都显着增加了人肝细胞培养物中凋亡细胞的百分比。结论是，原代大鼠和人肝细胞培养物对过氧化物酶体增殖物的反应不同。对 DNA 合成和细胞凋亡影响的差异支持了这样的假设：人类肝细胞对过氧化物酶体增殖物诱导的肝癌发生具有抵抗力。
The effects of the rodent hepatocarcinogens clofibric acid and diprofibrate on the activity of the peroxisomal fatty acyl-CoA oxidase, DNA synthesis, and apoptosis were compared in cultured rat and human hepatocytes. Rat hepatocytes expressed a 10-fold greater level of the peroxisomal fatty acyl-CoA oxidase compared to human hepatocytes. At the highest concentration (1.0 mM), both drugs induced a two- to threefold increase in this enzyme activity in both rat and human hepatocytes. Ciprofibrate (0.1 and 0.2 mM) caused a twofold increase in DNA synthesis in rat hepatocytes, whereas clofibric acid had no effect on DNA synthesis in these cells. In contrast, increasing concentrations of both clofibric acid and ciprofibrate produced inhibition of DNA synthesis in human hepatocytes. By using the terminal transferase dUTP-biotin nick end labeling technique, it was observed that 0.1 and 0.2 mM clofibric acid and ciprofibrate suppressed transforming growth factor-beta (TGF beta)-induced apoptosis by 50% in rat hepatocytes, but they had no effect on TGF beta-induced apoptosis in human hepatocytes. Although clofibric acid and ciprofibrate diminished TGF beta-induced apoptosis, they had no effect on the basal apoptotic levels in the rat hepatocyte cultures. However, both drugs significantly increased the percent of apoptotic cells in the human hepatocyte cultures. It is concluded that primary rat and human hepatocyte cultures respond differently to peroxisome proliferators. The differences in effects on DNA synthesis and apoptosis support the hypothesis that human liver cells are refractory to peroxisome proliferator-induced hepatocarcinogenesis.
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环丙贝特诱导肝癌过程中肝细胞增殖的评价。
影响因子：
9.7
作者：
Yeldandi,AV;Milano,M;Subbarao,V;Reddy,JK;Rao,MS
通讯作者：
Rao,MS
影响因子：
3.6
作者：
Palmer, CNA;Hsu, MH;Johnson, EF
通讯作者：
Johnson, EF
影响因子：
5.8
作者：
A. Bennett;G. Williams
通讯作者：
A. Bennett;G. Williams
对培养的肝细胞中计划外的 DNA 合成进行化学定量，作为快速筛选潜在化学致癌物的分析方法。
影响因子：
11.2
作者：
Althaus,FR;Lawrence,SD;Sattler,GL;Longfellow,DG;Pitot,HC
通讯作者：
Pitot,HC