• 1
    Pitot HC. Altered hepatic foci: their role in murine hepatocarci-nogenesis. Annu Rev Pharmacol Toxicol 1990; 30: 465500.
  • 2
    Schulte-Hermann R. Tumor promotion in the liver. Arch Toxicol 1985; 57: 147215.
  • 3
    Marsman DS, Popp JA. Biological potential of basophilic hepatocellular foci and hepatic adenoma induced by the peroxisome proliferator Wy-14,643. Carcinogenesis 1994; 15: 111117.
  • 4
    Deugnier YM, Charalambous P, Le Quillcuc D, Turlin B, Searle J, Brissot P, Pokell LW. et al. Preneoplastic significance of hepatic iron-free foci in genetic hemochromatosis: a study of 185 patients. Hepatology 1993; 8: 13631369.
  • 5
    Okuda K. Hepatocellular carcinoma: recent progress. Hepatology 1992; 15: 948963.
  • 6
    Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J. Response of liver foci in rats to hepatic tumor promoters. Toxicol Pathol 1982; 10: 6370.
  • 7
    Bursch W, Lauer B. Influence of liver tumor promoters on cell death by apoptosis in rat liver. Naunyn-Schmiedebergs Arch Pharmacol 1983; 322: R119.
  • 8
    Bursch W, Lauer B, Timmermann-Trosiener I, Barthel G, Schuppler J, Schulte-Hermann R. Controlled death (apoptosis) of normal and putative preneoplastic cells in rat liver following withdrawal of tumor promoters. Carcinogenesis 1984; 5: 453458.
  • 9
    Columbano A, Ledda-Columbano GM, Rao PM, Rajalakshmi S, Sarma DSR. Occurrence of cell death (apoptosis) in preneoplastic and neoplastic liver cells. Am J Pathol 1984; 116: 441446.
  • 10
    Schulte-Hermann R, Timmermann-Trosiener I, Barthel G, Bursch W. DNA synthesis, apoptosis, and phenotypic expression as determinants of growth of altered foci in rat liver during phenobarbital promotion. Cancer Res 1990; 50: 51275135.
  • 11
    Schulte-Hermann R, Bursch W, Grasl-Kraupp B. Active cell death (apoptosis) in liver biology and disease. In: BoyerJL, OcknerRK. eds. Progress in liver diseases. Philadelphia: Saunders, 1995: 195.
  • 12
    Grasl-Kraupp B, Bursch W, Ruttkay-Nedecky B, Wagner A, Lauer B, Schulte-Hermann R. Food reduction eliminates preneoplastic cells through apoptosis and antagonizes Carcinogenesis in rat liver. Proc Natl Acad Sci U S A 1994; 90: 99959999.
  • 13
    Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R. In situ detection of fragmented DNA (TUNEL-assay) fails to discriminate among apoptosis, necrosis and autolytic cell death, a cautionary note. Hepatology 1995; 21: 14651468.
  • 14
    Barnard JA, Lyons RM, Moses HL. The cell biology of transforming growth factor β. Biochim Biophys Acta 1990; 1032: 7987.
  • 15
    Michalopoulos GK. Liver regeneration: molecular mechanisms of growth control. FASEB J 1990; 4: 176187.
  • 16
    Bursch W, Oberhammer F, Jirtle RL, Askari M, Sedivy R, Grasl-Kraupp B, Purchio AF. Transforming growth factor-β1 as a signal for induction of cell death by apoptosis. Br J Cancer 1993; 67: 531536.
  • 17
    Mills JJ, Chari RS, Boyer IJ, Gould MN, Jirtle RL. Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol. Cancer Res 1995; 55: 979983.
  • 18
    Oberhammer F, Pavelka M, Sharma S, Tiefenbacher R, Purchio TR, Bursch W, Schulte-Hermann R. Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor-β1 Proc Natl Acad Sci U S A 1992; 89: 54085412.
  • 19
    Oberhammer F, Bursch W, Tiefenbacher R, Froschl G, Pavelka M, Purchio T, Schulte-Hermann R. Apoptosis is induced by transforming growth factor-β1 within 5 hours in regressing liver without significant fragmentation of the DNA. Hepatology 1993; 18: 12381246.
  • 20
    Huggins CH, Grand LC, Brillantes FP. Mammary cancer induced by a single feeding of polynuclear hydrocarbons, and its suppression. Nature 1961; 189: 204207.
  • 21
    Ochs H, Düsterberg B, Günzel P, Schulte-Hermann R. Effect of tumor promoting contraceptive steroids on growth and drug metabolizing enzymes in rat liver. Cancer Res 1986; 46: 12241233.
  • 22
    Yager JD, Zurlo J, Sewall CH, Lucier GW, He H. Growth stimulation followed by growth inhibition in livers of female rats treated with ethinylestradiol. Carcinogenesis 1994; 15: 21172123.
  • 23
    Goustin AC, Leof EB, Shipley GD, Moses HL. Growth factors and cancer. Cancer Res 1986; 46: 10151029.
  • 24
    Schulte-Hermann R. Two stage control of proliferation in rat liver by alpha-hexachlorocyclohexane. Cancer Res 1977; 37: 166171.
  • 25
    Grasl-Kraupp B, Waldhör T, Huber W, Schulte-Hermann R. Glutathione S-transferase isoenzyme patterns in different subtypes of enzyme-altered rat liver foci treated with the peroxisome proliferator nafenopin or with phenobarbital. Carcinogenesis 1993; 14: 24072412.
  • 26
    Kraupp-Grasl B, Huber W, Taper H, Schulte-Hermann R. Increased susceptibility of aged rats to hepatocarcinogenesis by the peroxisome proliferator nafenopin and the possible involvement of altered liver foci occurring spontaneously. Cancer Res 1991; 51: 666671.
  • 27
    Grasl-Kraupp B, Huber W, Just W, Gibson G, Schulte-Hermann R. Enhancement of peroxisomal enzymes, cytochrome P-452 and DNA synthesis in putative preneoplastic foci of rat liver treated with the peroxisome proliferator nafenopin. Carcinogenesis 1993; 14: 10071012.
  • 28
    Bursch W, Taper HS, Lauer B, Schulte-Hermann R. Quantitative histological and histochemical studies on the occurrence and stages of controlled cell death (apoptosis) during regression of rat liver hyperplasia. Virchows Arch B Cell Pathol Incl Mol Pathol 1985; 50: 153166.
  • 29
    Benedetti A, Jezequel AM, Orlandi F. Preferential distribution of apoptotic bodies in acinar zone 3 of normal human and rat liver. J Hepatol 1988; 7: 319324.
  • 30
    Schwall RH, Robbing K, Jardieu P, Chang L, Lai C, Terrell TG. Activin induces cell death in hepatocytes in vivo and in vitro. Hepatology 1993; 18: 347356.
  • 31
    Nakamura T, Tomita Y, Hirai R, Yamaoka K, Kaji K, Ichihara A. Inhibitory effect of transforming growth factor-beta on DNA synthesis of adult rat hepatocytes in primary culture. Biochem Biophys Res Commun 1985; 133: 10421050.
  • 32
    Carr BI, Hayashi I, Branum EL, Moses HL. Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type β transforming growth factor. Cancer Res 1986; 46: 23302334.
  • 33
    McMahon JB, Richards WL, del Campo AA, Song MH, Thorgeirsson SS. Differential effects of transforming growth factor-β on proliferation of normal and malignant rat liver epithelial cells in culture. Cancer Res 1986; 46: 46654671.
  • 34
    Russel WE, Coffey RJ, Ouellette AJ, Moses HL. Type β transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. Proc Natl Acad Sci USA 1988; 85: 51265130.
  • 35
    Fausto N. Protooncogenes and growth factors associated with normal and abnormal liver growth. Dig Dis Sci 1991; 36: 653658.
  • 36
    Francavilla A, Polimeno L, DiLeo A, Barone M, Ove P, Coetzee M, Eagon P. et al. The effect of estrogen and tamoxifen on hepatocyte proliferation in vivo and in vitro. Hepatology 1989; 9: 614620.
  • 37
    Bursch W, Taper H, Somer MP, Meyer S, Putz B, Schulte-Her-mann R. Histochemical and biochemical studies on the effect of the prostacyclin derivative iloprost on CCl4-induced lipid peroxidation in rat liver and its significance for hepatoprotection. Hepatology 1989; 9: 830836.
  • 38
    Coffey RJ, Kost LJ, Lyons RM, Moses HL, Russo NF. Hepatic processing of transforming growth factor β in the rat. J Clin Invest 1987; 80: 750757.
  • 39
    Wakefield LM, Winokur TS, Hollands RS, Christopherson K, Levinson AD, Sporn MB. Recombinant latent transforming growth factor β1 has a longer plasma half-life in rats than active transforming growth factor β1, and a different tissue distribution. J Clin Invest 1990; 86: 19761984.
  • 40
    Moses HL, Yang EY, Pietenpol JA. TGF-beta stimulation and inhibition of cell proliferation; new mechanistic insights. Cell 1990; 63: 245247.
  • 41
    Aldercreutz H, Tenhunen R. Some aspects of the interaction between natural and synthetic female sex hormones and the liver. Am J Med 1970; 49: 630648.
  • 42
    Duffy MJ, Duffy GJ. Estradiol receptors in human liver. J Steroid Biochem Mol Biol 1987; 9: 233235.
  • 43
    Baum JK, Hlotz F, Bookstein JJ, Klein EW. Possible association between benign hepatomas and oral contraceptives. Lancet 1973; 2: 926929.
  • 44
    Porter LE, Elm ME, Van Thiel DH. et al. Hepatic estrogen receptor in human disease. Gastroenterology 1987; 92: 735745.
  • 45
    Mishkin SY, Farber E, Ho RK, Mulay S, Mishkin S. Evidence for the hormone dependency of hepatic hyperplastic nodules: inhibition of malignant transformation after exogenous 17β-estra-diol and tamoxifen. Hepatology 1983; 3: 308316.
  • 46
    Wrana JL, Attisano L, Wieser R, Ventura F, Massague J. Mechanism of activation of the TGF-β receptor. Nature 1994; 370: 341347.
  • 47
    Wiseman H. Tamoxifen: new membrane-mediated mechanisms of action and therapeutic advances. Trends Pharmacol Sci 1994; 15: 8389.
  • 48
    Knabbe C, Lippmann ME, Wakefield LM, Flanders KG, Kasid A, Derynck R, Dickson RB. Evidence that transforming growth factor-β is a hormonally regulated negative growth factor in human breast cancer cells. Cell 1987; 48: 417428.
  • 49
    Butta A, MacLennan K, Flanders KG, Sacks NPM, Smith I, McKinna A, Dowsett M. et al. Induction of transforming growth factor β1 in human breast cancer in vivo following tamoxifen treatment. Cancer Res 1992; 52: 42614264.
  • 50
    Stewart BW. Mechanisms of apoptosis: integration of genetic, biochemical and cellular indicators. J Natl Cancer Inst 1994; 86: 12861296.
  • 51
    Han X, Liehr JG. Induction of covalent DNA adducts in rodents by tamoxifen. Cancer Res 1992; 52: 13601363.
  • 52
    Stenius U. Different inhibition of DNA synthesis by transforming growth factor β and phenobarbital on GST-P-positive and GST-P-negative hepatocytes. Carcinogenesis 1993; 14: 159161.
  • 53
    Engstrom PF, Levin B, Moertel CG, Schutt AA. Phase II trial of tamoxifen in hepatocellular carcinoma. Cancer 1990; 65: 26412643.
  • 54
    Farinati F, De Maria N, Fornasiero A, Salvagnini M, Fagiuoli S, Chiaramonte M, Naccarato R. Prospective controlled trial with antiestrogen drug tamoxifen in patients with unresectable hepatocellular carcinoma. Dig Dis Sci 1992; 37: 659662.
  • 55
    Melia WM, Johnson PJ, Williams R. Controlled clinical trial of doxorubicin and tamoxifen versus doxorubicin alone in hepatocellular carcinoma. Cancer Treat Rep 1987; 71: 12131216.
  • 56
    Recchia F, Passalacqua G, Rodorigo C, Belli L, Morgante A, Rabitti G. Hepatocellular carcinoma (HCC): the long-term response to tamoxifen. A clinical case report and review of the literature. Minerva Med 1989; 80: 13631366.
  • 57
    Wollenberg GK, Semple E, Quinn BA, Hayes MA. Inhibition of proliferation of normal, preneoplastic, and neoplastic rat hepatocytes by transforming growth factor-β Cancer Res 1987; 47: 65956599.
  • 58
    Fukuda K, Kojiro M, Chiu J-F. Induction of apoptosis by transforming growth factor-β1 in the rat hepatoma cell line McA-RH 7777: a possible association with tissue transglutaminase expression. Hepatology 1993; 18: 945953.
  • 59
    Lin J-K, Chou C-K. In vitro apoptosis in the human hepatoma cell line induced by transforming growth factor β1 Cancer Res 1992; 52: 385388.
  • 60
    Huggett AC, Ellis PA, Ford CP, Hampton LL, Rimoldi D, Thorgeirsson SS. Development of resistance to the growth inhibitory effects of transforming growth factor β1 during the spontaneous transformation of rat liver epithelial cells. Cancer Res 1991; 51: 59295936.
  • 61
    Zugmaier G, Paik S, Wilding G, Knabbe C, Bano M, Lupu R, Deschauer B. et al. Transforming growth factor β1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice. Cancer Res 1991; 51: 35903594.
  • 62
    Hard GC, Latropoulos MJ, Jordan K, Radi L, Kaltenberg OP, Imondi AR, Williams GM. Major differences in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl: CD (BR) rats. Cancer Res 1993; 53: 45344541.