Receptor Action and Liver Tumor Promotion

Nelson, K.

Abstract

It is the long range plan of this project to evaluate actions of receptors for toxic halogenated aromatics and estrogenically-active chemicals in relation to hepatotoxic potency of these compounds. These studies focus on receptor mediated effects on gene expression critical to tumor promotion using the rat two-stage model for hepatocarcinogenesis. The compounds of special interest are 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), structurally-related polychlorinated dibenzodioxins and dibenzofurans, diethylstilbestrol, 17Alpha-ethinylestradiol and Alpha-zearalanol. The objectives of these studies are to evaluate the quantitative relationships between dose of tumor promoter, receptor occupancy, critical changes in gene expression and histopathological alterations including preneoplastic lesions and tumor incidence. Furthermore, the time course of these changes are being investigated.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Intramural Research (Z01)
• Project #: 1Z01ES046004-01
• Application #: 4693227
• Support Year: 1
• Fiscal Year: 1985

Institution

• Name: U.S. National Inst of Environ Hlth Scis
• Country: United States

Publications

Xie, An; Walker, Nigel J; Wang, Desuo (2006) Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) enhances triggered afterdepolarizations in rat ventricular myocytes. Cardiovasc Toxicol 6:99-110

Haws, Laurie C; Su, Steave H; Harris, Mark et al. (2006) Development of a refined database of mammalian relative potency estimates for dioxin-like compounds. Toxicol Sci 89:4-30

Yoshizawa, Katsuhiko; Walker, Nigel J; Jokinen, Micheal P et al. (2005) Gingival carcinogenicity in female Harlan Sprague-Dawley rats following two-year oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. Toxicol Sci 83:64-77

Nyska, Abraham; Yoshizawa, Katsuhiko; Jokinen, Micheal P et al. (2005) Olfactory epithelial metaplasia and hyperplasia in female Harlan Sprague-Dawley rats following chronic treatment with polychlorinated biphenyls. Toxicol Pathol 33:371-7

Walker, Nigel J; Crockett, Patrick W; Nyska, Abraham et al. (2005) Dose-additive carcinogenicity of a defined mixture of ""dioxin-like compounds"". Environ Health Perspect 113:43-8

Brix, Amy E; Nyska, Abraham; Haseman, Joseph K et al. (2005) Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program. Toxicol Pathol 33:477-83

Yoshizawa, Katsuhiko; Marsh, Tiwanda; Foley, Julie F et al. (2005) Mechanisms of exocrine pancreatic toxicity induced by oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley Rats. Toxicol Sci 85:594-606

Hailey, James R; Walker, Nigel J; Sells, Donald M et al. (2005) Classification of proliferative hepatocellular lesions in harlan sprague-dawley rats chronically exposed to dioxin-like compounds. Toxicol Pathol 33:165-74

Nyska, Abraham; Jokinen, Micheal P; Brix, Amy E et al. (2004) Exocrine pancreatic pathology in female Harlan Sprague-Dawley rats after chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. Environ Health Perspect 112:903-9

Toyoshiba, Hiroyoshi; Walker, Nigel J; Bailer, A John et al. (2004) Evaluation of toxic equivalency factors for induction of cytochromes P450 CYP1A1 and CYP1A2 enzyme activity by dioxin-like compounds. Toxicol Appl Pharmacol 194:156-68