High colony forming capacity of primary cultured hepatocytes as a dominant trait in hepatocarcinogenesis-susceptible and resistant mouse strains.
When hepatocytes isolated from mouse liver are cultivated in vitro, a small fraction of cells can survive, forming colonies, while most cells die within a few weeks. We compared the colony forming capacity of hepatocytes in three mouse strains; two strains susceptible for hepatocarcinogenesis, C3H/HeJ (C3) and DBA/2J mice (D2), and one resistant strain, C57BL/6J mice (B6). The colony forming capacity was about 3:2:1 for D2, C3 and B6 at the 4th week after start of culture, indicating that this capacity correlated with the susceptibility to tumor induction. When the colony forming capacity was compared in F1 hybrids between the three strains, the high colony forming capacity was dominant, again resembling the trait for hepatocarcinogenesis. In F1 hybrids between the two susceptible strains, the colony numbers were more than those of the parental strains, indicating the high colony forming capacity of the two susceptible strains to be additive. During 4 weeks of culture period, the cells continuously proliferated, but fairly large numbers of cells died, some showing characteristics of apoptosis and others of lysis. Although the proliferation rate was not different among the three strains until the 2 week time point, it was significantly lower in B6 than in C3 or D2 strains by the 4th week. On the other hand, the cell death rate was lower in D2 cells than in B6 or C3 cells after 2 weeks. These results indicate that the genetic background affects proliferation and death rates of cultured hepatocytes, which may be related to the different colony forming capacity of these three strains.
Yoshie
M
M
Department of Pathology, Asahikawa Medical College, Nishikagura, Japan.
Nishimori
H
H
Lee
G H
GH
Ogawa
K
K
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D008099:Liver / Q000166:cytology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D013045:Species Specificity