Carcinogenicity of TCDD in Laboratory Animals: Implications for Risk Assessment

Abbott B. , and Birnbaum L. (1990). “TCDD-induced altered expression of growth factors may have a role in producing cleft palate and enhancing the incidence of clefts after coadministration of retinoic acid and TCDD.” Toxicol. Appl. Pharmacol. 106: 418–432.

Abernethy D.J. , Greenlee W.F. , Huband J.C. , and Boreiko C.J. (1985). “2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) promotes the transformation of C3H/10T1/2 cells.” Carcinogenesis. 6: 651–653.

Abraham K. , Krowke R. , and Neubert D. (1988). “Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Arch. Toxicol. 62: 359–368.

Arcos J.C. , Conney A.H. , and Buu-Hoi N.P. (1961). “Induction of microsomal enzyme synthesis by polycyclic aromatic hydrocarbons of different molecular sizes.” J. Biol. Chem. 236: 1291.

Astroff B. , Rowlands C. , Dickerson R. , and Safe S. (1990). “2,3,7,8-Tetra chlorodibenzo-p-dioxin inhibition of 17β-estradiol-induced increases in rat uterine epidermal growth factor receptor binding activity and gene expression.” Mol. Cell. Endocrin. 70: 247–252.

Barrett J.C. (1992). “Multistage carcinogenesis.” In: Mechanisms of Carcinogenesis in Risk Identification ( Vanio H. , Magee P.N. , McGregor D.B. , McMichael A.J. , eds.). IARC, WHO, Lyon, France. pp. 115–134.

Barrett J.C. , and Wiseman R.W. (1987). “Cellular and molecular mechanisms of multistep carcinogenesis: Relevance to carcinogen risk assessment.” Environ. Health Perspect. 76: 65–70.

Bars R.G. , and Elcombe C.R. (1991). “Dose-dependent acinar induction of cytochromes P450 in rat liver. Evidence for a differential mechanism of induction of P4501A1 by β-naphthaflavone and dioxin.” Biochem. J. 277: 577–580.

Barter R.A. , and Klaassen C.D. (1992). “UDP-glucuronosyltransferase inducers reduce thyroid hormone levels in rats by an extrathyroidal mechanism.” Toxicol. Appl. Pharmacol. 113: 36–42.

Bastomsky C.H. (1977). “Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Endocrinology. 101: 292–296.

Beguinot L. , Hanover J.A. , Ito S. , Richert M.D. , Willingham M.C. , and Pastan I. (1985). “Phorbol esters induce internalization without degradation of unoccupied epidermal growth factor receptors.” Proc. Natl. Acad. Sci. 82: 2774–2778.

Bock K.W. (1991). “Roles of UDP-glucuronyltransferases in chemical carcinogenesis.” Crit. Rev. Biochem. Mol. Biol. 26(2): 129–150.

Burchell B. , Nebert D.W. , Nelson D.R. , Bock K.W. , Iyanagi T. , Jansen P.L.M. , Lancet D. , Mulder G.J. , Chowdhury J.R. , Siest G. , Tephly T.R. , and Mackenzie P.I. (1991). “The UDP glucuronlytransferase gene superfamily: Suggested nomenclature based on evolutionary divergence.” DNA Cell Biol. 10(7): 487–494.

CALIFORNIA DEPARTMENT OF HEALTH SERVICES. (1985). “Health effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds. Response to public comments.” California Scientific Review Panel Discussions. September.

Carpenter G. (1987). “Receptors for epidermal growth factor and other polypeptide mitogens.” Ann. Rev. Biochem. 56: 881–914.

Carpenter G. , and Cohen S. (1979). “Epidermal growth factor.” Ann. Rev. Biochem. 48: 193–216.

Choi E. , Toscano D. , Ryan J. , Reidel N. , and Toscano W. (1991). “Dioxin induces transforming growth factor-α in human keratinocytes.” J. Biol. Chem. 266: 9591–9597.

Clark G. , Tritscher A. , Maronpot R. , Foley J. , and Lucier G. (1991a). “Tumor promotion by TCDD in female rats.” In: Banbury Report 35: Biological Basis for Risk Assessment of Dioxin and Related Compounds (M. Gallo, R. Scheuplein, and K. Van Der Heijden, eds.). Cold Spring Harbor Laboratory. pp. 389–404.

Clark G.C. , Taylor M.J. , Tritscher A.M. , and Lucier G.W. (1991b). “Tumor necrosis factor involvement in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated endotoxin hypersensitivity in C57BL/6J mice congenic at the Ah locus.” Toxicol. Appl. Pharmacol. 111: 422–431.

Clark G. , Tritscher A. , Bell D. , and Lucier G. (1992). “Integrative approach for evaluating species and interindividual differences in responsiveness to dioxins and structural analogs.” Environ. Health Perspect. 98: 125–132.

Cochet C. , Gill G.N. , Meisenhelder J. , Cooper J.A. , and Hunter T. (1984). “C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity.” J. Biol. Chem. 259: 2553–2558.

Cohen G.M. , Bracken W.M. , Iyer R.P. , Berry D.L. , Selkirk J.K. , and Slaga T.J. (1979). “Anticarcinogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on benzo[a]pyrene and 7,12-dimethylbenz[a]anthrene tumor initiation and its relationship to DNA binding.” Cancer Res. 39: 4027–4033.

Conney A.H. (1982). “Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G.H.A.” Clowes Memorial Lecture. Cancer Res. 42: 4875–4917.

Cook J.C. , and Greenlee W.F. (1989). “Characterization of a specific binding protein for 2,3,7,8-tetrachlorodibenzo-p-dioxin in human thymic epithelial cells.” Mol. Pharmacol. 35: 713–719.

Dannan G.A. , Porubeck D.J. , Nelson S.D. , Waxman D.J. , and Guengerich F.P. (1986). “17β-Estradiol 2- and 4-hydroxylation catalyzed by developmental patterns, and alterations in gonadectomy.” Endocrinology 118: 1952–1960.

Della Porta G. , Dragani T.A. , Sozzi G. (1987). “Carcinogenic effects of infantile and lone-term 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment in the mouse.” Tumori 73: 99–107.

DeVITO M.J. , Umbreit T.H. , Thomas T. , and Gallo M.A. (1991). “An analogy between the actions of the Ah receptor and the estrogen receptor for use in the biological basis for risk assessment of dioxin.” In: Banbury Report 35: Biological Basis for Risk Assessment of Dioxin and Related Compounds (M.A. Gallo, R.J. Scheuplein, and K.A. Van Der Heijden, eds.). Cold Spring Harbor Laboratory. pp. 427–440.

DeVITO M.J. , Thomas T. , Martin E. , Umbreit T.H. , and Gallo M.A. (1992). “Antiestrogenic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Tissue specific regulation of estrogen receptor in CD1 mice.” Toxicol. Appl. Pharmacol. 113: 284–292.

DiGIOVANNI J. , Viaje A. , Berry D.L. , Slaga T. , and Juchau M.R. (1977). “Tumor initiating ability of TCDD and Aroclor 1254 in the two stage system of mouse skin carcinogenesis.” Bull. Environ. Contam. Toxicol. 18: 552–557.

Dragan Y.P. , Rizvi T. , Xu Y.H. , Holly J.R. , Bawa N. , Campbell H.A. , Maronpotand R.R. , and Pitot H.C. (1991). “An initiation-promotion assay in rat liver as a potential complement to the 2-year carcinogenesis bioassay.” Fund. Appl. Toxicol. 16: 525–547.

Dragan Y.P. , Xu X. , Goldsworthy T.L. , Campbell H.A. , Maronpot R.R. , and Pitot H.C. (1992). “Characterization of the promotion of altered hepatic foci by 2,3,7,8 tetrachlorodibenzo-p-dioxin in the female rat.” Carcinogenesis. 13(8): 1389–1395.

Eckl P.M. , Meyer S.A. , Whitcombe W.R. , and Jirtle R.L. (1988). “Phenobarbital reduces EGF receptors in the ability of physiological concentrations of calcium to suppress hepatocyte proliferation.” Carcinogenesis 9: 479–483.

Eisenfeld A.J. , Aten R. , Weinberger M.J. , and Haselbacher G. (1976). “Estrogen receptor in the mammalian liver.” Science. 191: 862–865.

EPA SCIENCE ADVISORY BOARD. (1984). Environmental Health Committee Transcripts. Science Advisory Board, Washington, DC. November 29.

EPA SCIENCE ADVISORY BOARD (1989). “Review of draft documents: A cancer risk-specific dose estimate for 2,3,7,8-TCDD and estimating risk exposure to 2,3,7,8-TCDD.” EPA SAB Ad Hoc Dioxin Panel, Washington, DC.

Farber E. (1984). “The multiple nature of cancer development.” Cancer Res. 44: 4217–4223.

Fernandez P. , and Safe S. (1992). “Growth inhibitory and antimitogenic activity of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) in T47D human breast cancer cells.” Toxicol-Lett. 61(2-3): 185–197.

Fingerhut M.A. , Halperin W.E. , Marlow D.A. , Placitelli L.A. , Honchar P.A. , Sweeny M.H. , Gireife A.L. , Dill P.A. , Steenland K. , and Suruda A.J. (1991). “Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.” New Engl. J. Med. 324: 212–218.

Flodstrom S. , and Ahlborg U.G. (1991). “Promotion of hepatocarcinogenesis in rats by PCDDs and PCDFs.” In: Banbury Report 35: Biological Basis for Risk Assessment of Dioxin and Related Compounds (M.A. Gallo, R.J. Scheuplein, and K.A. Van Der Heijden, eds.). Cold Spring Harbor Laboratory. pp. 405–414.

Flodstrom S. , and Ahlborg V.G. (1992). “Relative tumor promoting activity of some polychlorinated dibenzo-p-dioxin-, dibenzofuran-, and biphenyl congeners in female rats.” Chemosphere 25: 1(2): 169–172.

Gierthy J.F. , Lincoln D.W. , Kampick S.J. , Dickerman H.W. , Bradlow H.L. , Niwa T. , and Swaneck G.E. (1988). “Enhancement of 2- and 16-α-estradiol hydroxylation in MCF-7 human breast cancer cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Biochem. Biophys. Res. Commun. 157: 515–520.

Giri A.K. (1987). “Mutagenic and genotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin: A review.” Mutat. Res. 168: 241–248.

Goldstein J.A. , and Linko P. (1984). “Differential induction of two 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible forms of cytochrome P-450 in extrahepatic versus hepatic tissues.” Mol. Pharmacol. 25: 185–191.

Goldstein J.A. , and Safe S. (1989). “Mechanism of action and structure-activity relationships for the chlorinated dibenzo-p-dioxins and related compounds.” In: Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxins, and Related Products ( Kimbrough R.D. , Jensen A.A. eds.). Elsevier, New York. pp. 239–293.

Goodman D.G. , and Saver R.M. (1992). “Hepatotoxicity in female Sprague-Dawley rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) pathology working group reevaluation.” Regul. Toxicol. Pharmacol. 15: 245–252.

Graham M.J. , Lucier G.W. , Linko P. , Maronpot R.R. , and Goldstein J.A. (1988). “Increases in cytochrome P-450 mediated 17β-estradiol 2-hydroxylase activity in rat liver microsomes after both acute administration and subchronic administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a two-stage hepatocarcinogenesis model.” Carcinogenesis. 9(11): 1935–1941.

Greig J.B. , and Dematteis F. (1973). “Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on drug metabolism and hepatic microsomes of rats and mice.” Environ. Health Perspect. 5: 211–220.

Guengerich F.P. (1988). “Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy.” Cancer Res. 48: 2946–2954.

Harris M. , Zacharewski T. , Piskorska-Pliszczynska J. , Rosengren R. , and Safe S. (1990a). “Structure-dependent induction of aryl hydrocarbon hydroxylase activity in C57BL/6 mice by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related congeners: Mechanistic studies.” Toxicol. Appl. Pharmacol. 105: 243–253.

Harris M. , Zacharewski T. , and Safe S. (1990b). “Effects of 2,3,7,8-tetrachloro dibenzo-p-dioxin and related compounds on the occupied nuclear estrogen receptor in MCF-7 human breast cancer cell.” Cancer Res. 50: 3579–3584.

Hasemen J.K. , Huff J.E. , and Boorman G.A. (1984). “Use of historical control data in carcinogenicity in rodents.” Toxicol. Pathol. 12(2): 126–135.

Hayashi K. , and Sakamoto N. (1986). Dynamic Analysis of Enzyme Systems. Japan Scientific Societies Press, Tokyo.

Hebert C.D. , Harris M.W. , Elwell M.R. , and Birnbaum L.S. (1990). “Relative toxicity and tumor-promoting ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), and 1,2,3,4,7,8-hexachloro dibenzofuran (HCDF) in hairless mice.” Toxicol. Appl. Pharmacol. 102: 362–377.

Henry E.C. , and Gasiewicz T.A. (1987). “Changes in thyroid hormones and thyroxine glucuronidation in hamsters compared with rats following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Toxicol. Appl. Pharmacol. 89: 165–174.

Hill R.N. , Erdreich L.S. , Paynter O.E. , Roberts P.A. , Rosenthal S.L. , and Wilkinson C.F. (1989). “Thyroid follicular cell carcinogenesis.” Fund. Appl. Toxicol. 12: 629–697.

Hudson L.G. , Toscano W.A. Jr. , and Greenlee W.F. (1985). “Regulation of epidermal growth factor binding in human keratinocyte cell line by 2,3,7,8-tetrachloro dibenzo-p-dioxin.” Toxicol. Appl. Pharmacol. 77: 251–259.

Huff J.E. , Salmon A.G. , Hooper N.K. , and Zeise L. (1991). “Long-term carcinogenesis studies on 2,3,7,8-tetrachlorodibenzo-p-dioxin and hexachlorodibenzo-p-dioxins.” Cell Biol. and Toxicol. 7(1): 67–94.

Huff J.E. (1992). “2,3,7,8-TCDD: A potent and complete carcinogen in experimental animals.” Chemosphere 25: 173–176.

Ignar-Trowbridge D.M. , Nelson K.G. , Bidwell M.C. , Curtis S.W. , Washburn T.P. , McLACHLAN J.A. , Korach K.S. (1992). “Coupling of dual signaling pathways: Epidermal growth factor action involves the estrogen receptor.” Proc. Natl. Acad. Sci. 89(10): 4658–4662.

INTERNATIONAL AGENCY FOR RESEARCH ON CANCER. (IARC). (1982). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Suppl. 4: “Chemicals, industrial processes, and industries associated with cancer in humans.” WHO, Lyon, France. pp. 238–243.

INTERNATIONAL AGENCY FOR RESEARCH ON CANCER. (IARC). (1992). Mechanisms of Carcinogenesis in Risk Identification. WHO, Lyon, France.

Ito N. , Tatematsu M. , Nakanishi K. , Hasegawa R. , Takano T. , Imaida K. , and Ugiso T. (1980). “The effects of various chemicals on the development of hyperplastic liver nodules in hepatectomized rats treated with N-nitrosodiethylamine or N-2-fluorenlyacetamide.” Jpn. J. Cancer Res. 71: 832–842.

Ito N. , Tatematsu M. , Hasegawa R. , and Tsuda H. (1989). “Medium-term bioassay system for detection of carcinogens and modifiers of hepatocarcinogenesis utilizing the GST-P positive liver cell focus as an endpoint marker.” Toxicologic Pathol. 17(4 Part 1): 630–641.

Kedderis L.B. , Diliberto J.J. , Linko P. , Goldstein J.A. , and Birnbaum L.S. (1991). “Disposition of 2,3,7,8-tetrabromodibenzo-p-dioxin and 2,3,7,8-tetrachloro dibenzo-p-dioxin in the rat: Biliary excretion and induction of cytochromes CYP1A1 and CYP1A2.” Toxicol. Appl. Pharmacol. 111: 163–172.

Kitchin K.T. , and Woods J.S. (1979). “2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) effects on hepatic microsomal cytochrome P-448-mediated enzyme activities.” Toxicol. Appl. Pharmacol. 47: 537–546.

Kociba R.J. , Keyes D.G. , Beyer J.E. , Carreon R.M. , Wade C.E. , Dittenber D.A. , Kalnins R.P. , Frauson L.E. , Parks C.N. , Barnard S.D. , Hummel R.A. , and Humiston C.G. (1978). “Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats.” Toxicol. Appl. Pharmacol. 46: 279–303.

Kociba R. (1984). “Evaluation of the carcinogenic and mutagenic potential of 2,3,7,8-TCDD and other chlorinated dioxins.” In: Banbury Report 18: Biological Mechanisms of Dioxin Action (A. Poland and R. Kimbrough, eds.). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory. pp. 73–84.

Kohn M.C. , Lucier G.W. , and Portier C.J. (1993). “A mechanistic model of effects of dioxin on gene expression in the rat liver.” Toxicol. Appl. Pharmacol. 20: 138–154.

Kouri R.E. , Rude T.H. , Joglekar R. , Dansette P.M. , Jerina D.M. , Atlas S.A. , Owens I.A. , and Nebert D.W. (1978). “2,3,7,8-Tetrachlorodibenzo-p-dioxin as cocarcinogen causing 3-methylcholanthrene-initiated subcutaneous tumors in mice genetically “nonresponsive” at Ah locus.” Cancer Res. 38: 2722–2783.

Levin W. , Wood A. , Chang R. , Ryan D. , and Thomas P. (1982). “Oxidative metabolism of polycyclic aromatic hydrocarbons to ultimate carcinogens.” Drug Metab. Rev. 13: 555–580.

Li J.J. , and Li S.A. (1990). “Estrogen carcinogenesis in hamster tissues: A critical review.” Endocrine Rev. 11(4): 524–53.1.

Lin F.H. , Clark G. , Birnbaum L.S. , Lucier G.W. , and Goldstein J.A. (1991a). “Influence of the Ah locus on the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the hepatic epidermal growth factor receptor.” Mol. Pharmacol. 39: 307–313.

Lin F. , Stohs S. , Birnbaum L. , Clark G. , Lucier G. , and Goldstein J. (1991b). “The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the hepatic estrogen and glucocorticoid receptors in congenic strains of Ah responsive and Ah non-responsive C57BL/6J mice.” Toxicol. Appl. Pharmacol. 108: 129–139.

Lorenzen A. , and Okey A.B. (1991). “Detection and characterization of Ah receptor in tissue and cells from human tonsils.” Toxicol. Appl. Pharmacol. 107: 203–214.

Lucier G.W. (1991). “Humans are a sensitive species to some of the biochemical effects of structural analogs of dioxin.” Environ. Toxicol. Chem. 10: 727–735.

Lucier G.W. , Portier C. , and Gallo M. (1993). “Receptor mechanisms and dose response models for the effects of dioxins.” Environ. Hlth. Perspect. 10 (1): 36–45.

Lucier G.W. , McDANIEL O.S. , Hook G.E.R. , Fowler B. , Sonawane B.R. , and Faeder E. (1973). “TCDD-induced changes in rat liver microsomal enzymes.” Environ. Health Perspect. 5: 199–210.

Lucier G.W. , McDANIEL O.S. , and Hook G.E.R. (1974). “Nature of the enhancement of uridine diphosphate glucuronyltransferase activity by 2,3,7,8-tetrachloro dibenzo-p-dioxin in rats.” Biochem. Pharmacol. 24: 325–334.

Lucier G.W. , Lui E.M.K. , and Lamartiniere C.A. (1979). “Metabolic activation/deactivation reactions during perinatal development.” Environ. Health Perspect. 29: 7–16.

Lucier G.W. , Slaughter S.R. , Thompson C. , Lamartiniere C.A. , and Powell-Jones W. (1981), “Selective actions of growth hormone on rat liver estrogen binding proteins.” Biochem. Biophys. Res. Commun. 103: 872–879.

Lucier G.W. , Rumbaugh R.C. , McCOY Z. , Hass R. , Harvan D. , and Albro P. (1986). “Ingestion of soil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic enzyme activities in rats.” Fund. Appl. Toxicol. 6: 364–371.

Lucier G.W. , Nelson K.G. , Everson R.B. , Wong T.K. , Philpot R.M. , Tiernant T. , Taylor M. , and Sunahara G.I. (1987). “Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans.” Environ. Health Perspect. 76: 79–87.

Lucier G.W. , Tritscher A.M. , Goldsworthy T. , Foley J. , Clark G. , Goldstein J. , and Maronpot R.R. (1991). “Ovarian hormones enhance TCDD-mediated increases in cell proliferation and preneoplastic foci in a two stage model for hepatocarcinogenesis.” Cancer Res. 51: 1391–1397.

Lucier G.W. , Clark G. , Tritscher A. , Foley J. , and Maronpot R. (1992). “Mechanisms of dioxin tumor promotion: Implications for risk assessment.” Chemosphere. (In press).

Lundgren K. , Andries M. , Thompson C. , and Lucier G.W. (1986). “Dioxin treatment of rats results in increased in vitro induction of sister chromatid exchanges by alpha-naphthoflavone: An animal model for human exposure to halogenated aromatics.” Toxicol. Appl. Pharmacol. 85: 189–195.

Lundgren K. , Andries M. , Thomson C. , and Lucier G.W. (1987). “α-naphthoflavone metabolized by 2,3,7,8-tetrachloro-p-dioxin induced rat liver microsomes: A potent clastogen in Chinese hamster ovary cells.” Cancer Res. 47: 3662–3666.

Lundgren K. , Collman G.W. , Wang-Wuu S. , Tiernan T. , Taylor M. , Thompson C.L. , and Lucier G.W. (1988). “Cytogenetic and chemical detection of human exposure to polyhalogenated aromatic hydrocarbons.” Environ. Mol. Mutagen. 11: 1–11.

Mably T.A. , Moore R.W. , Goy R.W. , and Peterson R.E. (1992). “In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Toxicol. Appl. Pharmacol. 114: 108–117.

Mably T.A. , Theobald H.M. , Ingall G.B. , and Peterson R.E. (1990). “Hyper gastrinemia is associated with decreased gastric acid secretion in 2,3,7,8-tetrachloro dibenzo-p-dioxin treated rats.” Toxicol. Appl. Pharmacol. 106: 518–528.

Madhukar B.V. , Brewster D.W. , and Matsumura F. (1984). “Effects of in vivo administered 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor binding of epidermal growth factor in the hepatic plasma membrane of rat, guinea pig, mouse and hamster.” Proc. Natl. Acad. Sci. 81: 7407–7411.

Madhukar B.V. , Ebner K. , Matsumura F. , Bombick D.W. , Brewster D.W. , and Kawamoto T. (1988). “2,3,7,8-Tetrachlorodibenzo-p-dioxin causes an increase in protein kinases associated with epidermal growth factor receptor in the hepatic plasma membrane.” J. Biochem. Toxicol. 3: 261–277.

Manchester D.K. , Gorson S.K. , Golas C.L. , Roberts E.A. , and Okey A.B. (1987). “Ah receptor in human placenta: Stabilization by molybdate and characterization of binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and benzo[a]pyrene.” Cancer Res. 47: 4861–4868.

Maronpot R.R. , Montgomery C.A. , Boorman G.A. , and McCONNELL E.E. (1986). “National Toxicology Program Nomenclature for hepatoproliferative lesions of rats.” Toxicol. Pathol. 14(2): 263–273.

Maronpot R.R. , Pitot H.C. , and Peraino C. (1989). “Use of rat liver altered focus models for testing chemicals that have completed two-year carcinogenicity studies.” Toxicol. Pathol. 17(4 Part 1): 651–662.

Marti M. , Burwen S. , and Jones A. (1989). “Biological effects of epidermal growth factor, with emphasis on the gastrointestinal tract and liver: An update.” Hepatology. 9: 126–139.

Mastri C. , and Lucier G. (1983). “Actions of hormonally active chemicals in the liver.” In: Endocrine Toxicology ( Thomas J.A. , ed.). Raven Press, New York. pp. 335–355.

Metzler M. (1984). “Metabolism of stilbene estrogens and steroidal estrogens in relation to carcinogenicity.” Arch. Toxicol. 55: 104–109.

Miller E.C. , Miller J.A. , Brown R.R. , and MacDONALD J.C. (1958). “On the protective action of certain polycyclic aromatic hydrocarbons against carcinogenesis by aminoazo dyes and 2-acetylaminofluorene.” Cancer Res. 18: 469.

Moolgavkar S. , and Knudson A. (1981). “Mutation and cancer: A model for human carcinogenesis.” J. Natl. Cancer Inst. 66: 1037–1052.

Moore R.W. , Parsons J.A. , Bookstaff R.C. , and Peterson R.E. (1989). “Plasma concentrations of pituitary hormones in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats.” J. Biochem. Toxicol. 4: 165–172.

Moore R.W. , Potter C.L. , Theobald H.M. , Robinson J.A. , and Peterson R.E. (1985). “Androgenic deficiency in male rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Toxicol. Appl. Pharmacol. 79: 99–111.

Mukku V.R. (1984). “Regulation of epidermal growth factor receptor levels by thyroid hormone.” J. Biol. Chem. 259(10): 6543–6547.

Mukku V. , and Stancel G. (1985). “Regulation of epidermal growth factor receptor by estrogen.” J. Biol. Chem. 260: 9820–9824.

NATIONAL CANCER INSTITUTE. (1979a). “Bioassay of dibenzo-p-dioxin for possible carcinogenicity.” National Institutes of Health, Bethesda, M.D. NCI Tech. Rept. No. 122.

NATIONAL CANCER INSTITUTE. (1979b). “Bioassay of dichlorodibenzo-p-dioxin for possible carcinogenicity.” National Institutes of Health, Bethesda, M.D. NCI Tech. Rept. No. 123.

NATIONAL TOXICOLOGY PROGRAM. (NTP). (1980). “Bioassay of a mixture of 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin for possible carcinogenicity (gavage study).” U.S. DHHS, PHS, Research Triangle Park, N.C. Tech. Rept. Ser. No. 198.

NATIONAL TOXICOLOGY PROGRAM. (NTP). (1982a). “Bioassay of 2,3,7,8-tetrachloro dibenzo-p-dioxin for possible carcinogenicity (gavage study).” U.S. DHHS, PHS, Research Triangle Park, N.C. Tech. Rept. Ser. No. 201.

NATIONAL TOXICOLOGY PROGRAM. (NTP). (1982b). “Bioassay of 2,3,7,8-tetrachloro dibenzo-p-dioxin for possible carcinogenicity (dermal study).” U.S. DHHS, PHS, Research Triangle Park, N.C. Tech. Rept. Ser. No. 201.

NATIONAL TOXICOLOGY PROGRAM. (NTP). (1984). “Report of the NTP Ad Hoc Panel on Chemical Carcinogenesis Testing and Evaluation.” Board of Scientific Counselors, U.S. DHHS, PHS, Research Triangle Park, NC.

Nelson K. , Vickers A. , Sunahara G. , and Lucier G. (1988). “Receptor and DNA ploidy changes during promotion of rat liver carcinogenesis.” In: Tumor Promoters: Biological Approaches for Mechanistic Studies and Assay Systems. Progress in Cancer Research and Therapy, Vol. 34(R. Langenbach, E. Elmore, and J. Barrett, eds.). Raven Press, New York. pp. 387–405.

Nemoto N. , and Gelboin H.V. (1976). “Enzymatic conjugation of benzo[a]pyrene oxides, phenols and dihydrodiols with UDP-glucuronic acid.” Biochem. Pharmacol. 25: 1221–1226.

Okey A.B. , Denison M.S. , Prokipcak R.D. , Roberts E.A. , and Harper P.A. (1989). “Receptors of polycyclic aromatic hydrocarbons.” In: Biologie Prospective ( Galteau M.M. , Siest G. , and Henny J. eds.). John Libbey Eurotext, Paris. pp. 605–610.

Osborne R. , Cook J.C. , Dold K.M. , Ross L. , Gaido K. , and Greenlee W.F. (1988). “TCDD receptor: Mechanisms of altered growth regulation in normal and transformed human keratinocytes.” In: Progress in Cancer Research and Therapy, Vol. 34( Langenbach R. , Burrett J.C. , Elmore E. , eds.). Raven Press, New York. pp. 407–416.

Parkinson A. , and Hurwitz A. (1991). “Omeprazole and the induction of human cytochrome P-450: A response to concerns about potential adverse effects.” Gastroenterology. 100(4): 1157–1164.

Parkinson A. , Thomas P.E. , Ryan D.E. , Reik L.M. , Safe S.H. , Robertson L.W. , and Levin W. (1983). “Differential time course of induction of rat liver microsomal cytochrome P450 isozymes and epoxide hydrolase by Aroclor 1254.” Arch. Biochem. Biophys. 225: 203–215.

Pelkonnen O. , and Nebert D.W. (1982). “Metabolism of polycyclic aromatic hydrocarbons: Etiologic role in carcinogenesis.” Pharmacol. Rev. 34: 189–222.

Peraino C. , Staffeldt E.F. , and Ludeman V.A. (1981). “Early appearance of histochemically altered hepatocyte foci and liver tumors in female rats treated with carcinogens 1 day after birth.” Carcinogenesis. 2: 463–465.

Pitot H.C. , and Campbell H.A. (1987). “An approach to the determination of the relative potencies of chemical agents during the stages of initiation and promotion in multistage hepatocarcinogenesis in the rat.” Environ. Health Perspect. 76: 49–56.

Pitot H.C. , and Sirica A.E. (1980). “The stages of initiation and promotion in hepatocarcinogenesis.” Biochim. Biophys. Acta. 605: 191–215.

Pitot H.C. , Goldsworthy T.L. , Campbell H.A. , and Poland A. (1980). “Quantitative evaluation of the promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamine.” Cancer Res. 40: 3616–3620.

Pitot H.C. , Goldsworthy T.L. , Moran S. , Kennan W. , Glauert H.P. , Maronpot R.R. , and Campbell H.A. (1987). “A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose-response relationships to altered hepatic foci.” Carcinogenesis 8: 1491–1499.

Pitot H.C. , Campbell H.A. , Maronpot R.R. , Bawa N. , Rizvi T.A. , Xu YI-HUA , Sargent L. , Dragan Y. , and Pyron M. (1989). “Critical parameters in the quantitation of the stages of initiation, promotion, and progression in one model of hepatocarcinogenesis in the rat.” Toxicol. Pathol. 17(4 Part 1): 594–612.

Poland A. , and Glover E. (1973). “Studies on the mechanism of toxicity of chlorinated dibenzo-p-dioxins.” Environ. Health Perspect. 5: 245–252.

Poland A. , and Knutson J.C. (1982). “2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: Examination of the mechanism of toxicity.” Ann. Rev. Pharmacol. Toxicol. 22: 517–554.

Poland A. , Palen D. , and Glover E. (1982). “Tumor promotion by TCDD in skin of HRS/J mice.” Nature 300(5889): 271–273.

Popp J.A. , and Goldsworthy T.L. (1989). “Defining foci of cellular alteration in short-term and medium-term rat liver tumor models.” Toxicol. Pathol. 17(4 Part 1): 561–568.

Portier C.J. (1987). “Statistical properties of a two-stage model of carcinogenesis.” Environ. Health Perspect. 76: 125–132.

Portier C. , Tritscher A. , Kohn M. , Sewall C. , Clark G. , Edler L. , Hoel D. , and Lucier G. (1992). “Ligand/receptor binding for 2,3,7,8-TCDD: Implications for risk assessment.” Fund. Appl. Toxicol. 20: 48–56.

Pour P. , Kmoch N. , Greiser E. , Mohr U. , Althoff J. , and Cardesa A. (1976). “Spontaneous tumors and common diseases in two colonies of Syrian hamsters: I. Incidence and sites.” J. Natl. Cancer Inst. 56(5): 931–935.

Powell-Jones W. , Thompson C. , Raeford S. , Lucier G.W. (1981). “Effect of gonadectomy on the ontogeny of estrogen-binding components in the rat liver cytosol.” Endocrinology 109: 628–636.

Randerath K. , Putman K.L. , Randerath E. , Mason G. , Kelly M. , and Safe S. (1988). “Organ-specific effects of long-term feeding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8-pentachlorodibenzo-p-dioxin on I-compounds in hepatic and renal DNA of female Sprague-Dawley rats.” Carcinogenesis 9(12): 2285–2289.

Rao M.S. , Subbarao V. , Prasad J.D. , and Scarpelli D.C. (1988). “Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Syrian golden hamster.” Carcinogenesis 9(9): 1677–1679.

Roberts L. (1991). “Dioxin risks revisited.” Science 251: 624–626.

Romkes M. , Piskorska-Pliszczynska J. , and Safe S. (1987). “Effects of 2,3,7,8-tetra chlorodibenzo-p-dioxin on hepatic and uterine estrogen receptor levels in rats.” Toxicol. Appl. Pharmacol. 87: 306–314.

Romkes M. , and Safe S. (1988). “Comparative activities of 2,3,7,8-tetrachloro dibenzo-p-dioxin and progesterone on antiestrogens in the female rat uterus.” Toxicol. Appl. Pharmacol. 92: 368–380.

Sanders J.E. , Eigenberg D.A. , Bracht L.J. , Wang W.R. , and Van Zwieten J.J. (1988). “Thyroid and liver trophic changes in rats secondary to liver microsomal enzyme induction caused by an experimental leukotriene antagonist (L-649,923).” Toxicol. Appl. Pharmacol. 95: 378–387.

Sauer R.M. (1990). “2,3,7,8-Tetrachlorodibenzo-p-dioxin in Sprague-Dawley rats.” Submitted to the Maine Scientific Advisory Panel by Pathco, Inc., Ijansville, MD. March 13.

Sewall C.H. , and Lucier G.W. (1993). “2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) mediated changes in the epidermal growth factor receptor in a two-stage model for hepatocarcinogenesis in female rats.” Carcinogenesis (In press).

Shi Y.E. , and Yager J.D. (1989). “Effects of the liver tumor promoter ethinyl estradiol on epidermal growth factor-induced DNA synthesis and epidermal growth factor receptor levels in cultured rat hepatocytes.” Cancer Res. 49: 3574–3580.

Shiverick K.T. , and Muther T.F. (1982). “Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on serum concentrations and the uterotrophic actions of exogenous estrone in rats.” Toxicol. Appl. Pharmacol. 65: 170–176.

Shiverick K.T. , and Muther T.F. (1983). “2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) effects on hepatic microsomal steroid metabolism and serum estradiol of pregnant rats.” Biochem. Pharmacol. 32: 991–995.

Shu H.P. , Paustenbach D.J. , and Murray F.J. (1987). “A critical evaluation of the use of mutagenesis, carcinogenesis and tumor promotion data in a cancer risk assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Reg. Toxicol. Pharmacol. 7: 57–58.

Silbergeld E.K. , and Gasiewicz T.A. (1989). “Dioxins and the Ah receptor.” Am. J. Ind. Med. 16: 455–474.

Sims P. , and Grover P.L. (1974). “Epoxides in polycyclic aromatic hydrocarbon metabolism and carcinogenesis.” Adv. Cancer Res. 20: 165–274.

Slaga T.J. , Becker L. , Bracken W.M. , and Weeks C.E. (1979). “The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7,12-dimethyl benz[a]anthracene and benzo[a]pyrene skin tumor initiation.” Cancer Lett. 7: 51–59.

Slaga T.J. , Fischer S.M. , Weeks C.E. , Klein-Szanto A.J.P. , and Reiners J. (1982). “Studies on the mechanisms involved in multistage carcinogenesis in mouse skin.” J. Cell. Biochem. 18: 99–119.

Sloop T.C. , and Lucier G.W. (1987). “Dose-dependent elevation of Ah receptor binding by TCDD in rat liver.” Toxicol. Appl. Pharmacol. 88: 329–337.

Squire R.A. (1980). “Pathologic evaluations of selected tissues from the Dow chemical TCDD and 2,4,5-T rat studies.” Submitted to Carcinogen Assessment Group, U.S. Environmental Protection Agency on August 15 under contract no. 68-01-5092.

Stoscheck C. , and King L. (1986). “Role of epidermal growth factor in carcinogenesis.” Cancer Res. 46: 1030–103.

Sunahara G. , Lucier G. , McCOY Z. , Bresnick E. , Sanchez E. , and Nelson K. (1989). “Characterization of 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decreases in dexamethasone binding to rat hepatic cytosolic glucocorticoid receptor.” Mol. Pharmacol. 36: 239–247.

Sunahara G.I. , Nelson K.G. , Wong T.K. , and Lucier G.W. (1988). “Decreased human birth weights after in utero exposure to PCBs and PCDFs are associated with decreased placental EGF-stimulated receptor autophosphorylation capacity.” Mol. Pharmacol. 32: 572–578.

Sutter T.R. , Guzman K. , Dold K.M. , and Greenlee W.F. (1991) “Targets for dioxin: Genes for plasminogen activator inhibitor-2 and interleukin-1β.” Science 254: 415–417.

Sutter T.R. , and Greenlee W.F. (1992). “Classification of members of the Ah gene battery.” Chemosphere 25: 223–226.

Swenberg J.A. , Richardson F.C. , Baucheron J.A. , Deal F.H. , Belinsky S.A. , Charbonneau M. , and Short B.G. (1987). “High- to low-dose extrapolation: Critical determinants involved in the dose response of carcinogenic substances.” Environ. Health Perspect. 76: 57–64.

Tephly T.R. , and Burchell B. (1990). “UDP-glucuronlytransferases: A family of detoxifying enzymes.” TIPS Rev. 11: 276–279.

Thakker D.R. , Yagi H. , Levin W. , Wood A.W. , Conney A.H. , and Jerina D.M. (1985). “Polycyclic aromatic hydrocarbons: Metabolic activation to ultimate carcinogens.” In: Bioactivation of Foreign Compounds ( Anders M.W. , ed.). Academic Press, Inc., New York. pp. 177–242.

Tritscher A.M. , Goldstein J.A. , Portier C.J. , McCOY Z. , Clark G.C. , and Lucier G.W. (1992). “Dose-response relationships for chronic exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin in a rat tumor promotion model: Quantification and immunolocalization of CYP1A1 and CYP1A2 in the liver.” Cancer Res. 52: 3436–3442.

Turteltaub K.W. , Felton J.S. , Gledhill B.L. , Vogel J.S. , Southon J.R. , Caffee M.W. , Finkel R.C. , Nelson D.E. , Proctor I.D. , and Davis J.C. (1990). “Accelerator mass spectrometry in biomedical dosimetry: Relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA.” Proc. Natl. Acad. Sci. 87: 5288–5292.

Umbreit T.H. , and Gallo M.A. (1988). “Physiological implications of estrogen receptor modulation by 2,3,7,8,-tetrachlorodibenzo-p-dioxin.” Toxicol. Lett. 42: 5–14.

Vanden Heuvel J.P. , Lucier G.W. (1992). “Environmental toxicology of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.” Environ. Health Perspect. 100: 189–200.

Vanden Heuvel J.P. , Lucier G.W. , Clark G.C. , Tritscher A.M. , Greenlee W.F. , Bell D.A. (1992). “Use of reverse-transcription polymerase chain reaction to quantitate mRNA for dioxin-responsive genes in the low-dose region in rat liver.” Chemosphere. (In press).

Vecchi A. , Sironi M. , Canegrati M.A. , Recchia M. , and Garatini S. (1983). “Immuno suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxylase.” Toxicol. Appl. Pharmacol. 68: 434–441.

Velu T. (1990). “Structure, function and transforming potential of the epidermal growth factor receptor.” Mol. Cell. Endocrin. 70: 205–216.

Vickers A. , and Lucier G. (1991). “Estrogen receptor, epidermal growth factor and cellular ploidy in elutriated subfractions of hepatocytes during liver promotion by 17α-ethinylestradiol in rats.” Carcinogenesis. 12: 391–399.

Vickers A.E.M. , Nelson K. , McCOY Z. , and Lucier G.W. (1989). “Changes in estrogen receptor, DNA ploidy, and estrogen metabolism in rat hepatocytes during a two-stage model for hepatocarcinogenesis using 17-ethinylestradiol as a promoting agent.” Cancer Res. 49: 6512–6520.

Wahba Z.Z. , Lawson T.A. , and Stohs S.J. (1988). “Induction of hepatic DNA single strand breaks in rats by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).” Cancer Lett. 29: 281–286.

Wahba Z.Z. , Lawson T.A. , Murray W.J. , and Stohs S.J. (1989). “Factors influencing the induction of DNA single strand breaks in rats by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).” Toxicology 58: 57–69.

Wassom J.S. , Huff J.E. , and Loprieno N. (1977). “A review of the genetic toxicology of chlorinated dibenzo-p-dioxins.” Mutat. Res. 47: 141–160.

Wattenberg L.W. , and Leong J.L. (1970). “Inhibition of the carcinogenic action of benzo(a)pyrene by flavones.” Cancer Res. 30: 1922–1925.

Wattenberg L.W. (1978). “Inhibition of chemical carcinogenesis.” J. Natl. Cancer Inst. 60: 11–18.

Wattenberg L.W. (1985). “Chemoprevention of cancer.” Cancer Res. 45: 108.

Wheatley D.N. (1968). “Enhancement and inhibition of the induction by 7,12-dimethylbenz-(a)anthracene of mammary tumors in female Sprague-Dawley rats.” Br. J. Cancer. 22: 787–797.

Whitlock J.P. Jr. (1990). “Genetic and molecular aspects of 2,3,7,8-tetrachloro dibenzo-p-dioxin action.” Ann. Rev. Pharmacol. Toxicol. 30: 251–277.

Williams G.M. (1989). “The significance of chemically-induced hepatocellular altered foci in rat liver and application to carcinogen detection.” Toxicologic Pathol. 17(4 Part 1): 663–674.

Wong T.K. , Domin B.A. , Bent P.E. , Blanto T.E. , Anderson M.W. , and Philpot R.M. (1986). “Correlation of placental microsomal activities with protein detected by antibodies to rabbit cytochrome P-450 isozyme 6 in preparations from humans exposed to polychlorinated biphenyls, quarterphenyls, and dibenzofurans.” Cancer Res. 46: 999–1004.

Yang J.-H. , Thraves P. , Dritschilo A. , and Rhim J.S. (1992). “Neoplastic transformation of immortalized human keratinocytes by 2,3,7,8-tetrachlorodibenzo-p-dioxin.” Cancer Res. 52: 3478–3482.

Zacharewski T. , Harris M. , and Safe S. (1991). “Evidence for a possible mechanism of action of the 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decrease of nuclear estrogen receptor levels in wild-type and mutant Hepa 1c1c7 cells.” Biochem. Pharmacol. 41: 1931–1939.

Zacharewski T. , Harris M. , Biegel L. , Morrison V. , Merchant M. , and Safe S. (1992). “6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) as an antiestrogen in human and rodent cancer cell lines: Evidence for the role of the Ah receptor.” Toxicol. Appl. Pharmacol. 113: 311–318.

Zeise L. , Huff J.E. , Salmon A.G. , and Hooper N.K. (1990). “Human risks from 2,3,7,8-tetrachlorodibenzo-p-dioxin and hexachlorodibenzo-p-dioxins.” In: Advances in Modern Environmental Toxicology, Vol. 17. Princeton Scientific Publishing Co., Inc., Princeton, NJ, pp. 293–342.