Species differences in the interaction between CCl4 reactive metabolites and liver DNA or nuclear protein fractions.
Species differences in the interaction between CCl4 reactive metabolites and liver DNA or nuclear protein fractions.
复制标题
CCl4 反应性代谢物与肝脏 DNA 或核蛋白组分之间相互作用的物种差异。
DOI：
10.1093/carcin/10.2.289
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发表时间：
1989
期刊：
影响因子：
4.7
通讯作者：
Castro,JA
中科院分区：
文献类型：
--
作者：
Castro,GD;DíazGómez,MI;Castro,JA
据报道，CCI4 是几种小鼠品系、叙利亚金仓鼠的肝脏致癌物，但不是斯普拉格-道利大鼠的肝脏致癌物。 CCI4 是一种实验性致癌物，尽管 CCI4 反应性代谢物与肝脏 DNA 共价结合，但尚无令人信服的致突变性证据。考虑到已知的 C3H 小鼠、叙利亚金仓鼠和 Sprague-Dawley 大鼠对 CCI4 的敏感性，我们在此描述了在体内或体外通过核制剂激活反应性代谢物后 CCI4 反应性代谢物与肝脏 DNA 和核蛋白的共价结合 (CB) 强度之间关系的研究。无论在体内还是体外，CCI4对肝脏的致癌作用强度和CCI4反应性代谢物的CB与总DNA的CB之间均不存在相关性。致癌性和 CB 与总核蛋白（体内或体外）之间存在良好的相关性。核蛋白分级分离研究表明，当核制剂在存在或不存在 NADPH 的情况下激活 CCI4 时，CCI4 反应性代谢物的 CB 与组蛋白和非组蛋白均相关。酸性和残留核蛋白是与 CCI4 反应性代谢物相互作用的最喜欢的目标。CB 与这些核蛋白级分和 CCI4 致癌性之间存在良好的相关性。发现了三个物种。
CCI4has been reported to be a liver carcinogen for several mice strains, for Syrian Golden hamsters, but not for Sprague-Dawley rats. CCI4is an experimental carcinogen for which no convincing evidence of mutagenicity is available despite the fact that CCI4reactive metabolites bind covalently to liver DNA. Here we describe studies on the relationship between the intensities of the covalent binding (CB) of CCI4reactive metabolites to liver DNA and nuclear proteins eitherin vivoorin vitroafter activation to reactive metabolites by nuclear preparations, considering the known susceptibility of the C3H mice, Syrian Golden hamsters and Sprague-Dawley rats to CCI4. There was no correlation between the intensity of CCI4carcinogenic effects on the liver and CB of CCI4reactive metabolites to total DNA eitherin vitroorin vivo. A good correlation between carcinogenicity and CB to total nuclear proteins (in vivoorin vitrowas found. Nuclear protein fractionation studies revealed CB of CCI4reactive metabolites to both histone and non-histone proteins when nuclear preparations activated CCI4either in the presence or absence of NADPH. Acidic and residual nuclear proteins were the favorite targets of the interaction with CCI4reactive metabolites. A good correlation between CB to these nuclear protein fractions and CCI4carcinogenicity in the three species was found.