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International Journal of Hepatology
Volume 2011 (2011), Article ID 424356, 9 pages
Research Article

Unique Properties of Hepatocarcinogenesis-Resistant DRH Rat Hepatocytes Linked or Not Linked to the Drh1 Locus on Rat Chromosome 1

Department of Pathology, Section of Oncology, Asahikawa Medical College, 2-1-1-1 East, Midorigaoka, Asahikawa 078-8510, Japan

Received 18 February 2011; Revised 23 April 2011; Accepted 19 May 2011

Academic Editor: Shigeru Marubashi

Copyright © 2011 Norikazu Hashimoto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.