Hashimoto Norikazu, Yamamoto Masahiro, Miyakoshi Masaaki, Tanaka Hiroki, Ogawa Katsuhiro
Department of Pathology, Section of Oncology, Asahikawa Medical College, 2-1-1-1 East, Midorigaoka, Asahikawa 078-8510, Japan.
Int J Hepatol. 2011;2011:424356. doi: 10.4061/2011/424356. Epub 2011 Jul 25.
Hepatocarcinogenesis-resistant DRH rats exhibit few and small preneoplastic hepatocytic lesions during hepatocarcinogenesis, of which traits have been assigned to two major chromosomal regions, Drh1 and Drh2. In this study, hepatocytes from DRH.F344-Drh1, a congenic strain in which the Drh1 chromosomal region was replaced with that of F344 rats, were compared to hepatocytes from Donryu (original strain), DRH, and F344 rats. Although DRH hepatocytes exhibited low proliferation and p38 dephosphorylation after lead nitrate (LN) treatment despite cytokine and Cox2 activation, DRH.F344-Drh1 hepatocytes exhibited high responses, as did Donryu and F344 hepatocytes. Moreover, although DRH hepatocytes were resistant to hepatotoxins, DRH.F344-Drh1 hepatocytes were as sensitive to hepatotoxins as Donryu and F344 hepatocytes. However, DRH.F344-Drh1 hepatocytes like DRH hepatocytes proliferated at lower rates in vitro and contained smaller nuclei than Donryu and F344 hepatocytes. Thus, low responses to LN and resistance to hepatotoxins in DRH hepatocytes were linked to the Drh1 locus, while low proliferation in vitro and small nuclear size were not linked to the Drh1 locus.
肝癌发生抗性DRH大鼠在肝癌发生过程中表现出很少且很小的癌前肝细胞病变，这些特征已归因于两个主要染色体区域，即Drh1和Drh2。在本研究中，将DRH.F344-Drh1（一种将Drh1染色体区域替换为F344大鼠染色体区域的近交系）的肝细胞与来自Donryu（原种系）、DRH和F344大鼠的肝细胞进行了比较。尽管在细胞因子和Cox2激活的情况下，DRH肝细胞在硝酸铅（LN）处理后表现出低增殖和p38去磷酸化，但DRH.F344-Drh1肝细胞表现出高反应，Donryu和F344肝细胞也是如此。此外，尽管DRH肝细胞对肝毒素具有抗性，但DRH.F344-Drh1肝细胞对肝毒素的敏感性与Donryu和F344肝细胞相同。然而，与DRH肝细胞一样，DRH.F344-Drh1肝细胞在体外的增殖率较低，并且细胞核比Donryu和F344肝细胞小。因此，DRH肝细胞对LN的低反应和对肝毒素的抗性与Drh1基因座有关，而体外低增殖和小核尺寸与Drh1基因座无关。
