title: Effects of carcinogens on hormonal regulation of gene expression in primary cultures of adult rat hepatocytes.
abstract: The report utilizes knowledge of the regulation of tyrosine aminotransferase (TAT) activity in rat liver as the basis for the development of a model system for investigating the effects of carcinogens on gene expression. A protocol utilizing primary monolayer cultures of adult rat hepatocytes was employed. The addition of dexamethasone resulted in a 5-fold induction of TAT activity; adding glucagon along with dexamethasone gave a 12-fold induction. The chemicals tested for possible effects on TAT induction were aflatoxins B1, B2, G1, G2, 2-acetylaminofluorene, 2-aminofluorene, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, and benzo[a]pyrene. Carcinogens inhibited the induction of TAT activity by dexamethasone alone or with glucagon in a dose dependent manner, and in general there was a correlation between inhibition of TAT induction and in vivo carcinogenic potency. In addition to the inhibition of TAT induction, the carcinogens similarly inhibited RNA synthesis and to a lesser extent, protein synthesis. The inhibition of these biochemical activities did not appear to be due to cell death.
mesh_terms: D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005796:Genes / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects; D014444:Tyrosine Transaminase / Q000235:genetics*
chemical_list: D000348:Aflatoxins; D002273:Carcinogens; D003907:Dexamethasone; D016604:Aflatoxin B1; D014444:Tyrosine Transaminase