Toxic effects of 7 beta-hydroxycholesterol on rat liver primary cultures, epithelial lines and co-cultures.
The toxic effects of 7 beta-hydroxycholesterol (7 beta-OHC) on cultures and co-cultures of rat hepatocytes, rat liver epithelial cell lines, and rat liver fibroblast lines were investigated. Hepatocytes in primary culture or co-cultured with proliferative epithelial cells, were not affected by the presence of 7 beta-OHC at a concentration of 400 microM over a period of 72 hours. In contrast, proliferative cultures of liver epithelial cell lines and liver fibroblast lines were killed by 50 microM 7 beta-OHC within the first 24 hours. Established liver epithelial cells (hyperploid) were more sensitive to 7 beta-OHC than the same line at early passages (diploid). When hepatocytes and liver epithelial cells were co-cultured and treated with 100 microM 7 beta-OHC, only epithelial cells were lysed. A concentration of 50 microM 7 beta-OHC was toxic to co-cultures of liver epithelial cell and fibroblasts together. In a serum-free medium, the cytotoxic concentration of 7 beta-OHC was lower than that in the serum-supplemented medium. Thus, liver epithelial cells cultured alone or co-cultured with hepatocytes were killed at 12.5 microM and 50 microM 7 beta-OHC, respectively. Finally, cholesterol concentrations four-fold that of 7 beta-OHC antagonized the lethal effects of 7 beta-OHC in the serum-free medium.
Nordmann
P
P
Laboratoire de Biochimie Médicale, Faculté de Médecine, Dijon.
Diez-Ibanez
M
M
Chessebeuf-Padieu
M
M
Luu
B
B
Mack
G
G
Mersel
M
M
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000633:toxicity; D003176:Complement C3 / Q000378:metabolism; D004847:Epithelial Cells; D005347:Fibroblasts; D006888:Hydroxycholesterols / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014168:Transferrin / Q000378:metabolism
D000418:Albumins; D003176:Complement C3; D006888:Hydroxycholesterols; D014168:Transferrin; C011724:cholest-5-en-3 beta,7 alpha-diol; D002784:Cholesterol