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

• 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
• DOI: 10.1093/carcin/17.2.197
• EISSN: 1460-2180
• ISSN: 0143-3334

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.