Kootstra A
Nucleic Acids Res. 1982 May 11;10(9):2775-89. doi: 10.1093/nar/10.9.2775.
The modification of core histone proteins in mouse 10T1/2 cells and human lung epitheloid (A549) cells by B(a)PDE in vivo and in vitro was found to be similar. Only histones H2A and H3 were extensively modified. Also other proteins, possibly A24 protein and the minor histone H1 species seem to be binding relatively high levels of this ultimate carcinogen. Butyrate treatment which causes hyperacetylation of the core histones, did not change the specificity of B(a)PDE binding to core histones, nor did it affect the initial level of DNA modification. The acetylated species of histone H3 were all accessible to B(a)PDE, suggesting that these epsilon-amino-groups of the lysine residues are not the targets of the B(a)PDE. The rate of removal of B(a)P-DNA adducts was not affected by butyrate treatment in either normal human or XP fibroblasts. Furthermore the B(a)P-core histones were not preferentially removed from normal human fibroblast chromatin during a 24 h post-treatment incubation.
研究发现，苯并[a]芘二醇环氧化物（B(a)PDE）在体内和体外对小鼠10T1/2细胞及人肺上皮样（A549）细胞核心组蛋白的修饰作用相似。只有组蛋白H2A和H3被广泛修饰。此外，其他蛋白质，可能是A24蛋白和次要组蛋白H1种类似乎也结合了相对高水平的这种最终致癌物。导致核心组蛋白超乙酰化的丁酸盐处理，既未改变B(a)PDE与核心组蛋白结合的特异性，也未影响DNA修饰的初始水平。组蛋白H3的乙酰化种类都可被B(a)PDE作用，这表明赖氨酸残基的这些ε-氨基基团不是B(a)PDE的作用靶点。在正常人或着色性干皮病（XP）成纤维细胞中，丁酸盐处理均不影响苯并[a]芘-DNA加合物的去除速率。此外，在处理后24小时的孵育过程中，B(a)P-核心组蛋白并非优先从正常人成纤维细胞染色质中被去除。
