| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
National Institute of Environmental Health Sciences [G. W. L., A. T., J. F., G. C., J. G., R. M.] and Chemical Industry Institute of Toxicology [T. G.], Research Triangle Park, North Carolina 27709
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in rodents. However, liver tumor incidence is increased by TCDD in female Sprague-Dawley rats but not male rats in chronic carcinogen bioassays. Our studies have investigated this finding by evaluating histological and biochemical parameters in a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats (intact and ovariectomized), using diethylnitrosamine (DEN) as the initiating agent and TCDD as the promoting agent. Increases in 
-glutamyl transpeptidase-positive foci were greater in intact female rats than in ovariectomized (OVX) animals. For example, in intact rats receiving both DEN and TCDD, the percentage of liver occupied by -glutamyl transpeptidase-positive foci was 0.37, compared to 0.08 in OVX rats. Values for intact or OVX rats receiving either DEN or TCDD only were 0.04 or less. Similar results were obtained when using placental glutathione S-transferase to detect hepatic preneoplastic lesions. Cell proliferation data, obtained using bromodeoxyuridine in osmotic minipumps, were consistent with preneoplastic foci data in that the hepatocyte labeling index was increased in DEN/TCDD intact rats but not in DEN/TCDD OVX rats. Analysis of data from individual animals revealed a strong correlation (P < 0.01) between cell proliferation and placental glutathione S-transferase-positive foci/cm3 in liver. These findings did not reflect effects of ovariectomy on TCDD tissue distribution, since livers of OVX rats contained more TCDD than livers of intact rats, although both groups of rats received a dose of 1.4 µg TCDD/kg once every 2 weeks for 30 weeks. Hepatic cytochrome P-450d (IA2) was induced approximately 6–8-fold in all TCDD-treated groups, and the magnitude of induction was not influenced by ovariectomy. This cytochrome efficiently catalyzes metabolism of 17ß-estradiol to catechol estrogens. Our data suggest that ovarian hormones (probably estrogens) play a significant role in the hepatocarcinogenic actions of TCDD.
1 To whom requests for reprints should be addressed, at NIEHS, MD A3-02, P. O. Box 12233, Research Triangle Park, NC 27709.
Received 8/17/90. Accepted 12/17/90.
This article has been cited by other articles:
|
|
 |
|
  T. Simon, L. L. Aylward, C. R. Kirman, J. C. Rowlands, and R. A. Budinsky Estimates of Cancer Potency of 2,3,7,8-Tetrachlorodibenzo(p)dioxin Using Linear and Nonlinear Dose-Response Modeling and Toxicokinetics Toxicol. Sci., December 1, 2009; 112(2): 490 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Silkworth, E. A. Carlson, C. McCulloch, K. Illouz, S. Goodwin, and T. R. Sutter Toxicogenomic Analysis of Gender, Chemical, and Dose Effects in Livers of TCDD- or Aroclor 1254-Exposed Rats Using a Multifactor Linear Model Toxicol. Sci., April 1, 2008; 102(2): 291 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Walker Unraveling the Complexities of the Mechanism of Action of Dioxins Toxicol. Sci., February 1, 2007; 95(2): 297 - 299. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Popp, E. Crouch, and E. E. McConnell A Weight-of-Evidence Analysis of the Cancer Dose-Response Characteristics of 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) Toxicol. Sci., February 1, 2006; 89(2): 361 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Matthews, B. Wihlen, J. Thomsen, and J.-A. Gustafsson Aryl Hydrocarbon Receptor-Mediated Transcription: Ligand-Dependent Recruitment of Estrogen Receptor {alpha} to 2,3,7,8-Tetrachlorodibenzo- p-Dioxin-Responsive Promoters Mol. Cell. Biol., July 1, 2005; 25(13): 5317 - 5328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wyde, A. P. J. M. Braen, M. Hejtmancik, J. D. Johnson, J. D. Toft, J. C. Blake, S. D. Cooper, J. Mahler, M. Vallant, J. R. Bucher, et al. Oral and Dermal Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Induces Cutaneous Papillomas and Squamous Cell Carcinomas in Female Hemizygous Tg.AC Transgenic Mice Toxicol. Sci., November 1, 2004; 82(1): 34 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wyde, T. Cambre, M. Lebetkin, S. R. Eldridge, and N. J. Walker Promotion of Altered Hepatic Foci by 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 17{beta}-estradiol in Male Sprague-Dawley Rats Toxicol. Sci., August 1, 2002; 68(2): 295 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Buchanan, S. Ohsako, C. Tohyama, P. S. Cooke, and T. Iguchi Dioxin Inhibition of Estrogen-Induced Mouse Uterine Epithelial Mitogenesis Involves Changes in Cyclin and Transforming Growth Factor-{beta} Expression Toxicol. Sci., March 1, 2002; 66(1): 62 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C. Ou, R. B. Conolly, R. S. Thomas, Y. Xu, M. E. Andersen, L. S. Chubb, H. C. Pitot, and R. S. H. Yang A Clonal Growth Model: Time-course Simulations of Liver Foci Growth following Penta- or Hexachlorobenzene Treatment in a Medium-term Bioassay Cancer Res., March 1, 2001; 61(5): 1879 - 1889. [Abstract] [Full Text]
|
|
|
|
|
|
M. Viluksela, Y. Bager, J. T. Tuomisto, G. Scheu, M. Unkila, R. Pohjanvirta, S. Flodström, V.-M. Kosma, J. Mäki-Paakkanen, T. Vartiainen, et al. Liver Tumor-promoting Activity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in TCDD-sensitive and TCDD-resistant Rat Strains Cancer Res., December 1, 2000; 60(24): 6911 - 6920. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. M. Tritscher, J. Mahler, C. J. Portier, G. W. Lucier, and N. J. Walker Induction of Lung Lesions in Female Rats Following Chronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicol Pathol, November 1, 2000; 28(6): 761 - 769. [Abstract] [PDF]
|
|
|
|
|
|
B. J. Davis, E. A. McCurdy, B. D. Miller, G. W. Lucier, and A. M. Tritscher Ovarian Tumors in Rats Induced by Chronic 2,3,7,8-Tetrachlorodibenzo-p- Dioxin Treatment Cancer Res., October 1, 2000; 60(19): 5414 - 5419. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. D. Yager Chapter 3: Endogenous Estrogens as Carcinogens Through Metabolic Activation J Natl Cancer Inst Monographs, July 1, 2000; 2000(27): 67 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wyde, J. Seely, G. W. Lucier, and N. J. Walker Toxicity of Chronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Diethylnitrosamine-Initiated Ovariectomized Rats Implanted with Subcutaneous 17 {beta}-Estradiol Pellets Toxicol. Sci., April 1, 2000; 54(2): 493 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Regulations and Advisories Toxicology and Industrial Health, April 1, 2000; 16(3-5): 173 - 201. [PDF]
|
|
|
|
|
|
R. C. Sills, T. L. Goldsworthy, and S. D. Sleight Tumor-Promoting Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Phenobarbital in Initiated Weanling Sprague-Dawley Rats: A Quantitative, Phenotypic, and ras p21 Protein Study Toxicol Pathol, May 1, 1994; 22(3): 270 - 281. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
