Unique Properties of Hepatocarcinogenesis-Resistant DRH Rat Hepatocytes Linked or Not Linked to the Drh1 Locus on Rat Chromosome
著者
Hashimoto, Norikazu
Yamamoto, Masahiro
Miyakoshi, Masaaki
Tanaka, Hiroki
Ogawa, Katsuhiro
上位タイトル
International journal of hepatology
Vol.2011,
(2011.
)
,p.424356-
識別番号
ISSN
2090-3456
DOI
10.4061/2011/424356
抄録
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.
