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比较体外CYP1A1诱导和遗传毒性作为环境样品潜在有害影响指标的研究。

Comparison of CYP1A1 induction and genotoxicity in vitro as indicators of potentially harmful effects of environmental samples.

作者信息

Kopponen P, Törrönen R, Mäki-Paakkanen J, von Wright A, Kärenlampi S

机构信息

Department of Physiology, University of Kuopio, Finland.

出版信息

Arch Toxicol. 1994;68(3):167-73. doi: 10.1007/s002040050050.

Abstract

Cytochrome P450IA1 (CYP1A1) induction of Hepa-1 mouse and H4IIE rat hepatoma cell lines was compared using selected environmental samples. The results were in agreement for both cell lines: no induction was observed for the fly ash extract from peat combustion, an intermediate induction was found for the fly ash extract from biosludge combustion, and a strong induction was detected for natural peat extract. However, Hepa-1 responded to the samples more sensitively than did H4IIE: the half maximal induction (ED50) values for Hepa-1 were smaller than those for H4IIE. In a bacterial DNA repair assay without metabolic activation and in a mammalian sister chromatid exchange test in the presence of metabolic activation the samples were virtually non-genotoxic. Thus the CYP1A1-inducing potency and genotoxicity of the samples were not correlated. In light of these results, the CYP1A1 induction test might be a useful addition to conventional genotoxicity tests, which may fail to detect potentially harmful compounds/mixtures.

摘要

使用选定的环境样品比较了细胞色素P450IA1(CYP1A1)对Hepa-1小鼠和H4IIE大鼠肝癌细胞系的诱导作用。两种细胞系的结果一致:泥炭燃烧产生的粉煤灰提取物未观察到诱导作用,生物污泥燃烧产生的粉煤灰提取物有中等程度的诱导作用,天然泥炭提取物有强烈的诱导作用。然而,Hepa-1对样品的反应比H4IIE更敏感:Hepa-1的半数最大诱导(ED50)值小于H4IIE的。在无代谢活化的细菌DNA修复试验和有代谢活化的哺乳动物姐妹染色单体交换试验中,样品实际上无遗传毒性。因此,样品的CYP1A1诱导能力和遗传毒性不相关。鉴于这些结果,CYP1A1诱导试验可能是对传统遗传毒性试验的有益补充,传统遗传毒性试验可能无法检测到潜在有害的化合物/混合物。

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