Since previous investigations on the genotoxicity of 4-hydroxynonenal (HNE) were carried out with prokaryotic systems or eukaryotic cell lines which may not adequately reflect the response of cells in vivo due to differences in the metabolism, the genotoxic potential of HNE was further evaluated in primary cells (hepatocytes) and cell clones of cerebral endothelial cells expressing specific functions, i.e. blood-brain barrier (BBB) and capillary formation associated phenotypes. Treatment of hepatocytes with HNE induced statistically significant levels of SCE at concentrations >/=0.1 microM, micronuclei at concentrations >/=1 microM and chromosomal aberrations at a concentration of 10 microM. Treatment of cloned cerebral microvascular endothelial cells induced significantly elevated levels of chromosomal aberrations at concentrations >/=1 microM and micronuclei at concentrations >/=10 microM in both cEC phenotypes, compared to the controls. Additionally, cytotoxicity was observed at a concentration of 50 microM HNE and was significantly higher in type II cells. These results indicate that cells expressing differentiated functions representative for the in vivo situation react more sensitive to HNE than cell lines, and may reflect the sensitivity of the target cells. The different response with respect to the endpoints of genotoxicity tested most probably depends on the different metabolizing capacities and thus the action of different metabolites of HNE.

中文翻译：

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HNE的遗传毒性。

由于先前对4-羟基壬烯醛（HNE）的遗传毒性的研究是利用可能由于代谢差异而无法充分反映体内细胞反应的原核系统或真核细胞系进行的，因此在2007年进一步评估了HNE的遗传毒性潜力。原代细胞（肝细胞）和脑内皮细胞的细胞克隆表达特定功能，即血脑屏障（BBB）和毛细血管形成相关表型。用HNE处理肝细胞在浓度> / = 0.1 microM中诱导统计学显着水平的SCE，在浓度> / = 1 microM中诱导微核，在浓度10 microM时引起染色体畸变。浓度>>时，对克隆的脑微血管内皮细胞的治疗可导致染色体畸变水平显着升高 与对照相比，两种cEC表型中的浓度为== 1 microM和微核浓度> / = 10 microM。另外，在50 microM HNE的浓度下观察到细胞毒性，在II型细胞中明显更高。这些结果表明，表达代表体内情况的分化功能的细胞比细胞系对HNE的反应更为敏感，并且可能反映了靶细胞的敏感性。关于所测试的遗传毒性终点的不同反应最可能取决于不同的代谢能力，并因此取决于HNE的不同代谢物的作用。在浓度为50 microM HNE时观察到细胞毒性，并且在II型细胞中明显更高。这些结果表明，表达代表体内情况的分化功能的细胞比细胞系对HNE的反应更敏感，并且可能反映了靶细胞的敏感性。关于测试的遗传毒性终点的不同反应最可能取决于不同的代谢能力，并因此取决于HNE的不同代谢物的作用。在浓度为50 microM HNE时观察到细胞毒性，并且在II型细胞中明显更高。这些结果表明，表达代表体内情况的分化功能的细胞比细胞系对HNE的反应更为敏感，并且可能反映了靶细胞的敏感性。关于测试的遗传毒性终点的不同反应最可能取决于不同的代谢能力，并因此取决于HNE的不同代谢物的作用。