Use of primary cultures of adult rat hepatocytes to investigate mechanisms of action of nafenopin, a hepatocarcinogenic peroxisome proliferator.
The effect of nafenopin upon primary cultures of adult rat hepatocytes has been investigated. Nafenopin treatment resulted in a proliferation of peroxisomes within the cultured cells. This proliferation was the result of an increase in both the number and size of the peroxisomes. Nafenopin treatment also caused an increased level of thymidine incorporation into the cultures, which was a consequence of replicative DNA synthesis rather than DNA repair. Finally, nafenopin appeared to delay the appearance of gamma-glutamyltranspeptidase activity within the cultured cells. Consequently three effects of nafenopin upon the liver were reproduced using monolayers of adult rat hepatocytes, which suggests that this culture system may be useful to further investigate the molecular processes underlying peroxisome proliferation, and their involvement in the hepatocarcinogenicity of peroxisome proliferators.
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D006918:Hydroxyurea / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D009255:Nafenopin / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D011422:Propionates; D009255:Nafenopin; D004247:DNA; D005723:gamma-Glutamyltransferase; D013936:Thymidine; D006918:Hydroxyurea