Mechanism of chromium(VI) carcinogenesis
Mechanism of chromium(VI) carcinogenesis
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六价铬致癌机制
DOI：
--
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发表时间：
1989
影响因子：
3.9
通讯作者：
R. Floyd
中科院分区：
文献类型：
--
作者：
K. Wetterhahn;J. Hamilton;J. Aiyar;K. Borges;R. Floyd
由于铬（VI）在体外生理条件下对DNA不起反应，因此致癌铬（VI）化合物损伤DNA的能力取决于细胞氧化还原组分的存在，这些组分将铬（VI）还原为能够与DNA相互作用的活性物质。我们研究了谷胱甘肽和过氧化氢在铬（VI）诱导的DNA损伤中的作用。在与铬（VI）反应时，谷胱甘肽产生铬（V）和谷胱甘肽硫基自由基反应中间体，而过氧化氢产生铬（V）和羟基自由基。在谷胱甘肽存在下，DNA与铬（VI）的反应导致铬和谷胱甘肽与DNA结合，而很少或没有DNA链断裂。在过氧化氢存在下，DNA与铬（VI）的反应产生8-羟基脱氧鸟苷加合物和广泛的DNA链断裂，在没有显着的Cr-DNA加合物形成。这些结果表明，铬（VI）诱导的DNA损伤的性质将强烈依赖于反应性中间体，如铬（V），谷胱甘肽巯基自由基，和羟基自由基，产生的细胞成分在铬（VI）代谢的活性。为了评估铬（VI）诱导的DNA损伤影响DNA正常模板功能的能力，我们研究了铬（VI）对体内鸡胚肝脏中各种基因的稳态mRNA水平的影响，并将其影响与观察到的DNA损伤水平进行比较。铬（VI）诱导的DNA-蛋白质和DNA链间交联在鸡胚肝脏在体内和抑制5-氨基乙酰丙酸合成酶和细胞色素P-450 mRNA表达的诱导卟啉药物。相比之下，铬（VI）增加了这两个诱导型基因的基础表达水平，但对组成型白蛋白、β-肌动蛋白和伴白蛋白基因的表达几乎没有影响。DNA损伤的形成和修复的时间过程与基因表达变化的时间过程的比较表明，铬（VI）可以在形成DNA交联之前形成单加合物，并且铬（VI）诱导的DNA损伤可以靶向某些类别的基因并导致其表达的变化。
Since chromium(VI) is unreactive toward DNA under physiological conditions in vitro, the ability of carcinogenic chromium(VI) compounds to damage DNA depends on the presence of cellular redox components that reduce chromium(VI) to reactive species capable of interacting with DNA. We have examined the role of glutathione and hydrogen peroxide in chromium(VI)-induced DNA damage in vitro. Upon reaction with chromium(VI), glutathione produced chromium(V) and glutathione thiyl radical reactive intermediates, whereas hydrogen peroxide produced chromium(V) and hydroxyl radical. Reaction of DNA with chromium(VI) in the presence of glutathione resulted in binding of chromium and glutathione to DNA with little or no DNA strand breakage. Reaction of DNA with chromium(VI) in the presence of hydrogen peroxide produced the 8-hydroxydeoxy-guanosine adduct and extensive DNA strand breakage in the absence of significant Cr-DNA adduct formation. These results suggest that the nature of chromium(VI)-induced DNA damage will be strongly dependent on reactive intermediates such as chromium(V), glutathione thiyl radical, and hydroxyl radical, produced by cellular components active in chromium(VI) metabolism. In order to assess the ability of chromium(VI)-induced DNA damage to affect the normal template function of DNA, we investigated the effects of chromium(VI) on steady-state mRNA levels of various genes in chick embryo liver in vivo, and compared the effects to the levels of DNA damage observed. Chromium(VI) induced DNA-protein and DNA interstrand cross-links in chick embryo liver in vivo and suppressed the induction of 5-aminolevulinic acid synthase and cytochrome P-450 mRNA expression by porphyrinogenic drugs. In contrast, chromium(VI) increased the basal levels of expression of these two inducible genes, but had little or no effect on the expression of the constitutive albumin, β-actin, and conalbumin genes. Comparison of the time course of formation and repair of DNA damage with that of changes in gene expression suggests that chromium(VI) may form a mono-adduct prior to formation of DNA cross-links, and that chromium(VI)-induced DNA lesions may target certain classes of genes and lead to changes in their expression.
糖皮质激素受体与大鼠肝细胞核的结合发生在没有核转运的情况下。
DOI：
10.1016/0960-0760(93)90220-q
发表时间：
1993
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Miyashita,Y;Miller,M;Yen,PM;Harmon,JM;Hanover,JA;SimonsJr,SS
通讯作者：
SimonsJr,SS
化学性肝癌发生过程中肝脏酪氨酸转氨酶信使 RNA 水平的变化。
影响因子：
9.7
作者：
Huang,DP;Maine,AB;Chiu,JF
通讯作者：
Chiu,JF
致癌物质铬酸盐会造成 DNA 损伤，并抑制药物介导的鸡胚肝细胞中卟啉积累和葡萄糖醛酸化的诱导。
影响因子：
4.7
作者：
Tsapakos,MJ;Hampton,TH;Sinclair,PR;Sinclair,JF;Bement,WJ;Wetterhahn,KE
通讯作者：
Wetterhahn,KE