Ramagli L S, Capetillo S, Becker F F, Rodriguez L V
Carcinogenesis. 1985 Mar;6(3):367-75. doi: 10.1093/carcin/6.3.367.
Nonhistone chromosomal proteins (NHCP) from normal, regenerating rat liver, fetal liver, stages during acetylaminofluorene (AAF) and diethylnitrosamine (DEN) induced carcinogenesis, and resultant primary hepatocellular carcinomas (PHC) were analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). These studies sought to determine if changes in proteins putatively involved in catalyzing specific gene expression (NHCP) occur during liver cancer development that might be related to the malignant phenotype. NHCP extracted in high salt-urea buffers, analyzed by 2D-PAGE and silver staining were resolved into some 530-560 polypeptides. Increases in number of NHCP amounting to 8.4, 8.6 and 8.8%, respectively, were detected in AAF induced nodules (AAF-NOD), AAF-PHCs and DEN-PHCs when compared to normal chromatins. The majority of the 51 qualitative changes detected reflected cell cycling and/or reexpression of fetal-NHCP. Within the total changes, seven new NHCP were found only in AAF- and DEN-induced PHCs. Further, four NHCP with isoelectric points and relative molecular weights (pI/MW) of 5.62/19.3, 5.96/30.7, 6.25/46.6 and 8.16/53.5 occurring in both AAF- and DEN-PHC also were found in AAF-NOD, a carcinogenesis stage considered to represent premalignant nodules. Reciprocally, three NHCP of pI/mol.wt.: 6.81/34.0, 5.82/43.7 and 8.18/67.0 present in normal liver, disappeared in all carcinogen involved tissues analyzed. These findings indicate that while AAF and DEN exposure results in a number of qualitative NHCP changes specific for the particular carcinogen, a total of only ten changes, seven inductions and three losses, occurred in common during hepatocarcinogenesis induced by these diverse agents. At least four of these NHCP may prove critical inductions during malignant conversion or alternatively might serve as tumor markers since they appear first in a well characterized premalignant stage and persist in resultant tumors.
通过二维聚丙烯酰胺凝胶电泳（2D-PAGE）分析了来自正常、再生大鼠肝脏、胎儿肝脏、乙酰氨基芴（AAF）和二乙基亚硝胺（DEN）诱导致癌过程各阶段以及由此产生的原发性肝细胞癌（PHC）的非组蛋白染色体蛋白（NHCP）。这些研究旨在确定在肝癌发生过程中，假定参与催化特定基因表达的蛋白质（NHCP）是否发生变化，这些变化可能与恶性表型有关。用高盐-尿素缓冲液提取的NHCP，通过2D-PAGE和银染分析，可分辨出约530-560种多肽。与正常染色质相比，在AAF诱导的结节（AAF-NOD）、AAF-PHC和DEN-PHC中分别检测到NHCP数量增加了8.4%、8.6%和8.8%。检测到的51种定性变化中的大多数反映了细胞周期和/或胎儿NHCP的重新表达。在所有变化中，仅在AAF和DEN诱导的PHC中发现了7种新的NHCP。此外，在AAF-NOD（一个被认为代表癌前结节的致癌阶段）中也发现了在AAF和DEN-PHC中都出现的等电点和相对分子量（pI/MW）分别为5.62/19.3、5.96/30.7、6.25/46.6和8.16/53.5的4种NHCP。相反，正常肝脏中存在的等电点/分子量分别为6.81/34.0、5.82/43.7和8.18/67.0的3种NHCP，在所有分析的致癌物相关组织中均消失。这些发现表明，虽然AAF和DEN暴露会导致许多特定于特定致癌物的NHCP定性变化，但在这些不同试剂诱导的肝癌发生过程中，总共仅出现了10种变化，7种诱导和3种缺失。这些NHCP中至少有4种可能在恶性转化过程中被证明是关键诱导因素，或者可作为肿瘤标志物，因为它们首先出现在特征明确的癌前阶段并在最终肿瘤中持续存在。
