Summary
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a hepatocarcinogen in female rats but not male rats. Our studies, employing a two-stage model for hepatocarcinogenesis, reveal a significant difference between intact and ovariectomized (ovx) rats for the tumor-promoting activity of TCDD. In order to clarify the estrogen/TCDD interactions in this model with DEN (diethylnitrosamine) as initiating agent and TCDD as the promoting agent, we investigated two receptor systems known to be affected by TCDD-treatment and that are involved in hepatocyte proliferation. EGF-receptor binding is significantly decreased in intact but not ovx animals. Decrease in estrogen-receptor binding is also more pronounced in intact animals. Ovariectomy had no effect on the amount of induction of cytochromes P-450 1A1(c) and 1A2(d). Preneoplastic lesions (GGT-positive foci) were found at a much higher incidence in livers of intact rats than in ovx rats. TCDD markedly increased cell turnover (BrdU-labelling) only in intact rats. A long-term dose-response study showed, that the induction of P-450 1A2 correlates with the dose of TCDD. Our data suggest that ovarian hormones significantly enhance the tumor promoting activity of TCDD in the rat liver.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Kociba RJ, Keyes, DG, Beyer, JE, Carreon, RM, Wade CE, Dittenber, DA, Kalnins, RP, Frauson, LE, Park, CN, Barnard, SD, Hummel, RA, Humiston, CG (1978) Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzop-dioxinin rats. Toxicol Appl Pharmacol 46: 279–303.
National Toxicology Program (1982) Technical Report Series No. 102. Research Triangle Park, NC: National Toxicology Program.
Poland, A, Palen, D, Glover, E (1982) Tumor promotion by TCDD in skin of HRS/J mice. Nature (Lond) 300: 271–273.
Lucier, GW, Tritscher, A, Goldsworthy, T, Foley, J, Clark, G, Goldstein, J, Maronpot, R (1991) Ovarian hormones enhance 2,3,7,8tetrachlorodibenzo -p-dioxin-mediated increases in cell proliferation and preneoplastic foci in a two-stage model for rat hepatocarcinogenesis. Cancer Res 51: 1391–1397.
Metzler, M (1984) Metabolism of stilbene estrogens and steroidal estrogens in relation to carcinogenicity. Arch Toxicol 55: 104–109.
Popp, JA, Goldsworthy, TL (1989) Defining foci of cellular alteration in short-term and medium-term rat liver tumor models. Toxicol Pathol 17: 561–568.
Leung, H, Poland, A, Paustenbach, DJ, Murray, FJ, Andersen, ME (1990) Pharmacokinetics of [`2–5I]-2-lodo-3,7,8-trichlorodibenzo p-dioxin in mice: analysis with a physiological modeling approach. Toxicol and Appl Pharmacol 103: 411–419.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer-Verlag New York, Inc.
About this paper
Cite this paper
Tritscher, A.M., Clark, G.C., Lin, FH., Lucier, G.W. (1992). Ovarian Hormones Enhance the Carcinogenic Activity of 2,3,7,8-TCDD in Rats. In: Li, J.J., Nandi, S., Li, S.A. (eds) Hormonal Carcinogenesis. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-9208-8_51
Download citation
DOI: https://doi.org/10.1007/978-1-4613-9208-8_51
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4613-9210-1
Online ISBN: 978-1-4613-9208-8
eBook Packages: Springer Book Archive