An improved long-term culture of rat hepatocytes to detect liver tumour-promoting agents: results with phenobarbital.
Among various cocultures of hepatocytes with other cell types, we found that mouse embryonal cells (BALB/c 3T3) are more effective in maintaining rat hepatocytes in vitro. Because most human cancers are epithelial in origin, we thought that such a hepatocyte culture system could be used for the detection of tumour-promoting agents, most of which are inhibitors of gap-junctional intercellular communication. We, therefore, have examined the effect of the strong rat liver tumour promoter, phenobarbital, on the gap-junctional intercellular communication capacity of hepatocytes in long-term cultures. A single application of phenobarbital drastically inhibited the gap-junctional intercellular communication between hepatocytes in a coculture for only several hours, but treatment for 3 weeks provoked a constant decrease of gap-junctional intercellular communication (50%) throughout the treatment period. This type of long-term culture of rat hepatocytes may be usable in a rapid in vitro assay to detect tumour-promoting agents.
Mesnil
M
M
International Agency for Research on Cancer, Lyon, France.
Piccoli
C
C
Yamasaki
H
H
D000418:Albumins / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D017630:Connexins; D008099:Liver / Q000166:cytology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014168:Transferrin / Q000378:metabolism
D000418:Albumins; D002273:Carcinogens; D004396:Coloring Agents; D017630:Connexins; D008565:Membrane Proteins; D014168:Transferrin; D010634:Phenobarbital