Different inhibition of DNA synthesis by transforming growth factor beta and phenobarbital on GST-P-positive and GST-P-negative hepatocytes.
Hepatocyte resistance against inhibition of DNA synthesis by transforming growth factor beta 1 (TGF-beta 1) was studied in vitro. Hepatocytes were isolated from rats that had received diethylnitrosamine (DEN) for 6 weeks. The effect of TGF-beta 1 and phenobarbital (PB) on DNA synthesis in different cell populations was studied using bromodeoxyuridine (BrdU) incorporation and placental glutathione S-transferase (GST-P) as markers. It was found that GST-P-positive cells were resistant to the growth inhibitory effect of TGF-beta 1 and PB, whereas GST-P-negative cells were inhibited. It is concluded that resistance to TGF-beta 1-dependent growth control may develop early during DEN-induced hepatocarcinogenesis.
Stenius
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Department of Toxicology, National Institute of Occupational Health, Solna, Sweden.
D000818:Animals; D001973:Bromodeoxyuridine; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004052:Diethylnitrosamine; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D004052:Diethylnitrosamine; D004247:DNA; D005982:Glutathione Transferase; D001973:Bromodeoxyuridine; D010634:Phenobarbital