Growth modulation of hepatocytes and rat liver epithelial cells (WB-F344) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Modulation of DNA synthesis by 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) was studied in primary cultures of hepatocytes and in rat liver epithelial cells (WB-F344) to develop models for studies on the interactions between the activated Ah receptor and cellular growth control. In hepatocytes TCDD e...

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Bibliographic Details
Published in:	Carcinogenesis (New York) Vol. 17; no. 2; pp. 197 - 202
Main Authors:	Münzel, Peter, Bock-Hennig, Barbara, Schieback, Sylvia, Gschaidmeier, Harald, Beck-Gschaidmeier, Simone, Bock, Karl Walter
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-02-1996
Subjects:	Animals Biological and medical sciences Carcinogenesis, carcinogens and anticarcinogens Cell Division - drug effects Cell Line Chemical agents DNA - biosynthesis DNA - drug effects Drug Interactions Epidermal Growth Factor - pharmacology Estradiol - pharmacology Liver - cytology Liver - drug effects Liver - metabolism Male Medical sciences Polychlorinated Dibenzodioxins - pharmacology Proto-Oncogene Proteins c-fos - biosynthesis Proto-Oncogene Proteins c-jun - biosynthesis Rats Rats, Wistar RNA, Messenger - biosynthesis Tumors Cell culture Rat Growth Liver Rodentia DNA synthesis In vitro Carcinogen Ah receptor Vertebrata Mammalia Hepatocyte Animal C-Onc gene Established cell line Epithelial cell Molecular biology Mechanism of action
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Summary:	Modulation of DNA synthesis by 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) was studied in primary cultures of hepatocytes and in rat liver epithelial cells (WB-F344) to develop models for studies on the interactions between the activated Ah receptor and cellular growth control. In hepatocytes TCDD either positively or negatively modulated EGF-stimulated DNA synthesis. In the presence of ethlnylestradiol 10−12 M TCDD moderately increased EGF-stimulated DNA synthyesis (∼30%). In contrast, 10−9 M TCDD in the absence of ethlnylestradiol decreased DNA synthesis (∼30%). Analysis of variance revealed that the TCDD effects were highly significant. The response of ‘early genes’ of the jun/fos family and the corresponding proteins was also studied under these two conditions. In agreement with the DNA synthesis data, the level of c-Jun was increased or decreased in nuclear extracts. Further-more, DNA binding of Jun/Fos proteins, including c-Jun and Fra-1, was decreased under conditions of mitoinhibi-tion, while the level of Fra-1 in nuclear extracts was increased. In WB-F344 cells TCDDtreatment for 44 h increased DNA synthesis 2- to 3-fold in comparison with controls, based on measuring [3H]thymidine incorporation into DNA or on determining the nuclear labeling index with bromodeoxyuridine. This effect is probablydue to inhibition of high density growth arrest by TCDD. The proposed cellular models may be useful to elucidate the interactions between the activated Ah receptor and signaling pathways of growth homeostasis.
Bibliography:	istex:BEFD0FA49443FC9004AA27F941EDBD49B45F0279 1To whom correspondence should be addressed ark:/67375/HXZ-NX2P468W-D ArticleID:17.2.197 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0143-3334 1460-2180
DOI:	10.1093/carcin/17.2.197