Skip to main content
Log in

Tumor promotion in the liver

  • Review
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Abbreviations

HCH:

Hexachlorocyclohexane

HCB:

Hexachlorobenzene

PCB:

polychlorinated biphenyl

PBB:

polybrominated biphenyl

PB:

Phenobarbital

γ-GT:

γ-Glutamyl transferase

SER:

smooth endoplasmic reticulum

References

  1. Boutwell R.K (1974) The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol 2: 419–443

    Google Scholar 

  2. Pitot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605: 191–215

    Google Scholar 

  3. Farber E, Cameron R (1980) The sequential analysis of cancer development. Adv Cancer Res 31: 125–225

    Google Scholar 

  4. Sivak A (1979) Cocarcinogenesis. Biochim Biophys Acta 560: 67–89

    Google Scholar 

  5. Hecker E (1978) Co-carcinogene oder bedingt krebsauslösende Faktoren. Aktuelle neue Aspekte der Ätiologie menschlicher Tumoren und des molekularen Mechanismus der Krebsentstehung. Naturwissenschaften 65: 640–648

    Google Scholar 

  6. Hicks RM (1983) Pathological and biochemical aspects of tumor promotion. Carcinogenesis 4: 1209–1214

    Google Scholar 

  7. Diamond L, O'Brien T.G, Baird W.M. (1980) Tumor promoters and the mechanism of tumor promotion. Adv. Cancer Res 32: 1–74

    Google Scholar 

  8. Slaga TJ, Klein-Szanto AJP, Fischer SM, Weeks CE, Nelson K, Major S (1980) Studies on mechanism of action of antitumor-promoting agents: Their specificity in two-stage promotion. Proc Natl Acad Sci 77: 2251–2254

    Google Scholar 

  9. Fürstenberger G, Berry DL, Sorg B, Marks F (1981) Skin tumor promotion by phorbol esters is a two-stage process. Proc. Natl. Acad Sci 78: 7722–7726

    Google Scholar 

  10. Roe FJ, Carter RL, Mitchley BCV, Peto R, Hecker E (1972) On the persistence of tumor initiation and the acceleration of tumor progression in mouse skin tumorigenesis. Int J Cancer 9: 264–273

    Google Scholar 

  11. Hennings H, Shores R, Wenk ML, Spangler EF, Tarone R, Yuspa SH (1983) Malignant conversion of mouse skin tumors is increased by tumor initiators and unaffected by tumor promoters. Nature 304: 67–69

    Google Scholar 

  12. Wynder EL, Hoffmann D, McCoy GD, Cohen LA, Reddy BS (1978) Tumor promotion and cocarcinogenesis as related to man and his environment. In: Slaga T.J, Sivak A, Boutwell R.K. (eds) Carcinogenesis, Vol. 2: Mechanisms of tumor promotion and cocarcinogenesis. Raven Press New York 59–77, New York

    Google Scholar 

  13. Reddy BS, Weisburger JH, Wynder EL (1978) Bile salts as tumor promoters in Carcinogenesis, Vol 2: Mechanisms of tumor promotion and cocarcinogenesis. Slaga T.J, Sivak A, Boutwell R.K, (eds). Raven Press New York pp 453–464

    Google Scholar 

  14. Hicks RM, Chowaniec J, Wakefield JSJ (1978) Experimental induction of bladder tumors by a two-stage-system, in Carcinogenesis, Vol. 2: Mechanisms of tumor promotion and cocarcinogenesis. Slaga, T.J, Sivak A, Boutwell R.K. (eds). Raven Press, New York pp 475–490

    Google Scholar 

  15. Witschi HR, Morse CC (1983) Enhancement of lung tumor formation in mice by dietary butylated hydroxytuoluene: Dose-time relationships and cell kinetics. J Natl Cancer Inst 71: 859–865

    Google Scholar 

  16. Yokoro K, Nakano M, Ito A, Nagao K, Kodama Y, Hamada K (1977) Role of prolactin in rat mammary carcinogenesis: detection of carcinogenicity of low-dose carcinogens and of persisting dormant cancer cells. J Natl Cancer Inst 58: 1777–1783

    Google Scholar 

  17. Farber E (1982) Sequential events in chemical carcinogenesis. From: Cancer: A comprehensive treatise, Vol. 1 (2nd Edition). Becker F (ed) Plenum Publishing Corp

  18. Iversen UM, Iversen OH (1979) The carcinogenic effect of TPA (12-0-tetradecanoylphorbol-13-acetate) when applied to the skin of hairless mice. Virchos Arch B Cell Path 30: 33–42

    Google Scholar 

  19. Iversen OH (1981) Some critical thoughts on the two-stage theory of carcinogenesis. In: Biology of skin cancer, UICC Technical Report Series 63, Genf

  20. Bannasch P: Der Einfluß modifizierender Faktoren auf die Sequenz zellulärer Veränderungen bei der Hepatocarcinogenese. In: Tumor-Promotoren. Erkennung, Wirkungsmechanismen und Bedeutung. Bundesgesundheitsamt Berlin 1984, in press

  21. Hecker E (1976) Definitions and terminology in cancer (tumor) etiology. An analysis aiming at proposals for a current internationally standardized terminology. Z Krebsforsch 86: 219–230

    Google Scholar 

  22. Peraino C, Fry RJM, Staffeldt E. (1971) Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorene. Cancer Res 31: 1506–1512

    Google Scholar 

  23. Schulte-Hermann R (1974) Induction of liver growth by xenobiotic compounds and other stimuli. Crit Rev Toxicol 3: 97–158

    Google Scholar 

  24. Peraino C, Fry RJM, Staffeldt E, Kisieleski WE (1973) Effects of varying the exposure to phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigensis in the rat. Cancer Res 33: 2701–2705

    Google Scholar 

  25. Peraino C, Fry RJM, Staffeldt E, Christopher JP (1975) Comparative enhancing effects of phenobarbital, amorbarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res 35: 2884–2890

    Google Scholar 

  26. Peraino C, Fry RJM, Staffeldt E, Christopher JP (1977) Enhancing effects of phenobarbitone and butylated hydroxytoluene on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Fd Cosmet Toxicol 15: 93–96

    Google Scholar 

  27. Weisburger JH, Madison RM, Ward JM, Viguera C, Weisburger EK (1975) Modification of diethylnitrosamine liver carcinogenesis with phenobarbital but not with immunosuppression. J Natl Cancer Inst 54: 1185–1188

    Google Scholar 

  28. Mochizuki Y, Furukawa, K, Sawada N, Gotoh M (1981) Dose-dependent enhancing effect of phenobarbital on hepatocarcinogenesis initiated by diethylnitrosamine in the rat. Gann 72: 170–173

    Google Scholar 

  29. Kitagawa T, Hirakawa T, Ishikawa T, Nemoto N, Takayama S (1980) Induction of hepatocellular carcinoma in rat liver by initial treatment with benzo(a)pyrene after partial hepatectomy and promotion by phenobarbital. Toxicol Lett 6: 167–171

    Google Scholar 

  30. Schulte-Hermann R, Parzefall W (1981) Failure to discriminate initiation from promotion of liver tumors in a long-term study with the phenobarbital-type inducer α-hexachlorocyclohexane and the role of sustained stimulation of hepatic growth and monooxygenases. Cancer Res 41: 4140–4146

    Google Scholar 

  31. Schulte-Hermann R, Schuppler J, Timmermann-Trosiener I, Ohde G, Bursch W, Berger H (1983) The role of growth of normal and preneoplastic cell populations for tumor promotion in rat liver. Environ Health Perspect 50: 185–194

    Google Scholar 

  32. Pereira M, Herren SL, Britt A, Khoury MM (1982) Sex difference in enhancement of GGTase-positive foci by hexachlorobenzene and lindane in rat liver. Cancer Lett 15: 95–101

    Google Scholar 

  33. Deml E, Oesterle D (1982) Sex-dependent promoting effect of polychlorinated biphenyls on enzyme-altered islands induced by diethylnitrosamine in rat liver. Carcinogenesis 3: 1449–1453

    Google Scholar 

  34. Jensen RK, Sleight SD, Goodman JI, Aust SD, Trosko JE (1982) Polybrominated biphenyls as promoters in experimental-hepatocarcinogenesis in rats. Carcinogenesis 3: 1183–1185

    Google Scholar 

  35. Pitot HC, Goldsworthy T, Campbell HA, 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

    Google Scholar 

  36. Schulte-Hermann R, Schuppler J, Ohde G, Timmermann-Trosiener I (1982) Effect of tumor promoters on proliferation of putative preneoplastic cells in rat liver. Carcinogenesis 7, Hecker E. et al. (eds). Raven Press, New York pp 99–104

    Google Scholar 

  37. Taper HS (1978) The effect of estradiol-17-phenylpropionate and estradiol benzoate on N-nitrosomorpholine-induced liver carcinogenesis in ovariectomized female rats. Cancer 42: 462–467

    Google Scholar 

  38. Cameron RG, Imaida K, Tsuda H, Ito N (1982) Promotive effects of steroids and bile acids on hepatocarcinogensis initiated by diehtylnitrosamine. Cancer Res 42: 2426–2428

    Google Scholar 

  39. Yager JD, Campbell HA, Longnecker DS, Roebuck BD, Benoit MC (1984) Enhancement of hepatocarcinogenesis in female rats by ethinyl estradiol and mestranol but not estradiol. Cancer Res 44: 3862–3869

    Google Scholar 

  40. Mochizuki Y, Furukawa K, Sawada N (1982) Effects of various concentrations of ethyl-α-p-chlorophenoxyisobutyrate (clofibrate) on diethylnitrosamine-induced hepatic tumorigenesis in the rat. Carcinogenesis 3: 1027–1029

    Google Scholar 

  41. Ward JM, Rice JM, Creasia D, Lynch P, Riggs D (1983) Dis similar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice. Carcinogenesis 4: 1021–1029

    Google Scholar 

  42. Schulte-Hermann R (1979) Reactions of the liver to injury: Adaptation. In: Toxic Injury of the liver (Farber/Fisher eds), Marcel Dekker, New York pp 385–444

    Google Scholar 

  43. Schulte-Hermann R (1979) Adaptive liver growth induced by xenobiotic compounds: Its nature and mechanism. In: Mechanisms of Toxic Action on Some Target Organs; Arch. Toxicol., Suppl. 2 pp 113–124

  44. Ueda Y (1967) The relation between experimental liver carcinoma and liver cirrhosis induced by successive administration of p-dimethylaminoazobenzene and carbon tetrachloride. Tohoku J Exp Med 92: 109–140

    Google Scholar 

  45. Pound AW, McGuire LJ (1978) Influence of repeated liver regeneration on hepatic carcinogenesis by diethylnitrosamine in mice. Br J Cancer 37: 595–602

    Google Scholar 

  46. Solt DB, Cayama E, Tsuda H, Enomoto K, Lee G, Farber E (1983) Promotion of liver cancer development by brief exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or carbon tetrachloride. Cancer Res 43: 188–191

    Google Scholar 

  47. Lombardi B, Shinozuka H (1979) Enhancement of 2-acetylaminofluorene liver carcinogenesis in rats fed a choline-devoid diet. Int J Cancer 565–570

  48. Columbano A, Ledda GM, Rao PM, Rajalakshmi S, Sarma DSR (1982) Dietary orotic acid, a new selective growth stimulus for carcinogen altered hepatocytes in rat. Cancer Lett 16: 191–196

    Google Scholar 

  49. Ghoshal AK, Ahluwalia M, Farber E (1983) The rapid induction of liver cell death in rats fed a choline-deficient methionine-low diet. Natl. Cancer Inst 113: 309–314

    Google Scholar 

  50. Pound AW, McGuire LJ (1978) Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats. Br J Cancer 37: 585–594

    Google Scholar 

  51. Nakanishi K, Fukushima S, Hagiwara A, Tamano S, Ito N (1982) Organ-specific promoting effects of phenobarbital sodium and sodium saccharin in the induction of liver and urinary bladder tumors in male F344 rats. J Natl Cancer Inst 68: 497–500

    Google Scholar 

  52. Hiasa Y, Kitahori Y, Konishi N, Enoki N, Fujita T (1983) Effect of varying the duration of exposure to phenobarbital on its enhancement of N-bis(2-hydroxypropyl)nitrosamineinduced thyroid tumorigensis in male Wistar rats. Carcinogenesis 4: 935–937

    Google Scholar 

  53. Poland A, Palen D, Glover E (1982) Tumor promotion by TCDD in skin of HRS/J hairless mice. Nature 300: 272–273

    Google Scholar 

  54. Clemmesen J, Hjalgrim-Jensen S (1978) Is phenobarbital carcinogenic? A follow-up of 8078 epileptics. Ecotoxicol. Environ Saf 1: 457–470

    Google Scholar 

  55. Popper H (1979) Hepatic cancers in man: Quantitative perspectives. Environ Res 19: 482–494

    Google Scholar 

  56. Kerlin P, Davis GL, McGill DB, Weiland LH, Adson MA, Sheedy II, PF (1983) Hepatic adenoma and focal nodular hyperplasia: Clinical, pathologic, and radiologic features. Gastroenterology 84: 994–1002

    Google Scholar 

  57. Weiler E (1956) Die Änderung der serologischen Spezifität von Leberzellen der Ratte während der Cancerogenese durch p-Dimethylaminoazobenzol. Z Naturforsch 11 b: 31–37

    Google Scholar 

  58. Bannasch P, Moore MA, Klimek F, Zerban H (1982) Biological markers of preneoplastic foci and neoplastic nodules in rodent liver. Toxicol Pathol 10: 19–36

    Google Scholar 

  59. Rabes HM, Bücher T, Hartmann A, Linke I, Dünnwald M (1982) Clonal growth of carcinogen-induced enzyme-deficient preneoplastic cell populations in mouse liver. Cancer Res 42: 3220–3227

    Google Scholar 

  60. Scherer E, Hoffmann M, Emmelot P, Friedrich-Freksa H (1972) Quantiative study on foci of altered liver cells induced in the rat by a single dose of diethylnitrosamine and partial hepatectomy. J Natl Cancer Inst 49: 93–106

    Google Scholar 

  61. Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1982) Response of liver foci in rats to hepatic tumor promoters. Toxicol Pathol 10: 63–70

    Google Scholar 

  62. Williams GM (1982) Phenotypic properties of preneoplastic rat liver lesions and applications to detection of carcinogens and tumor promoters. Toxicol Pathol 10: 3–10

    Google Scholar 

  63. Hanigan HM, Pitot HC (1982) Isolation of γ-glutamyl transpeptidase positive hepatocytes during the early stages of hepatocarcinogenesis in the rat. Carcinogenesis 3: 1349–1354

    Google Scholar 

  64. Ledda GM, Sells MA, Yokoyama S, Lombardi B (1983) Metabolic properties of isolated rat liver cell preparations enriched in epithelial cells other than hepatocytes. Int J Cancer 31: 231–237

    Google Scholar 

  65. Yaswen P, Hayner N.T, Fausto N. (1984) Isolation of oval cells by centrifugal elutriation and comparison with other cell types purified from normal and preneoplastic livers. Cancer Res 44: 324–331

    Google Scholar 

  66. Fischer G, Ullrich D, Katz N, Bock K.W, Schauer A. (1983) Immunohistochemical and biochemical detection of uridined-iphosphate-glucuronyltransferase (UDP-GT) activity in putative preneoplastic liver foci. Virchows Arch Cell Pathol. 42: 193–200

    Google Scholar 

  67. Klimek F, Mayer D, Bannasch P. (1984) Biochemical microanalysis of glycogen content and glucose-6-phosphate dehydrogenase activity in focal lesions of the rat liver induced by N-nitrosomorpholine. Carcinogenesis 5: 265–268

    Google Scholar 

  68. Kitahara A, Satoh K, Sato K (1983) Properties of the increased glutathione S-transferase a form in rat preneoplastic hepatic lesions induced by chemical carcinogens. Biochem Biophys Res Comm 112: 20–28

    Google Scholar 

  69. Schulte-Hermann R Roome N Timmermann-Trosiener I, Schuppler J (1984) Immunocytochemical demonstration of a phenobarbital-inducible cytochrome P450 in putative preneoplastic foci of rat liver. Carcinogenesis 5: 149–153

    Google Scholar 

  70. Aström A, DePierre J.W, Eriksson L. (1983) Characterization of drug-metabolizing systems in hyperplastic nodules from the livers of rats receiving 2-acetylaminofluorene in their diet. Carcinogenesis 4: 577–581

    Google Scholar 

  71. Kuhlmann WD, Krischan R, Kunz W, Guenthner TM, Oesch F (1981) Focal elevation of liver microsomal epoxide hydrolase in early preneoplastic stages and its behaviour in the further course of hepatocarcinogenesis. Biochem Biophys Res Commun 98: 417–423

    Google Scholar 

  72. Bannasch P, Hacker HJ, Klimek F Mayer, D. (1984) Hepatocellular glycogenosis and related pattern of enzymatic changes during hepatocarcinogensis. In: Advances in enzyme regulation. Vol. 22. Weber G (ed). Pergamon Press Oxford, New York

    Google Scholar 

  73. Friedrich-Freksa H, Gössner W, Börner P (1969) Histochemische Untersuchungen der Cancerogenese in der Rattenleber nach Dauergaben von Diäthylnitrosamin. Z Krebsforsch 72: 226–239

    Google Scholar 

  74. Reinacher M., Eigenbrodt E, Gerbracht U, Zenk G, Timmermann-Trosiener I, Bentley P, Waechter F, Schoner W, Schulte-Hermann R: Pyruvate kinase isoenzymes in altered foci and carcinoma of rat liver. (in press)

  75. Schulte-Hermann R, Ohde G, Schuppler J, Timmermann-Trosiener I (1981) Enhanced proliferation of putative preneoplastic cells in rat liver following treatment with the tumor promoters phenobarbital, hexachlorocyclohexane, steroid compounds and nafenopin. Cancer Res 41: 2556–2562

    Google Scholar 

  76. Taper HS, Lans M, de Gerlache LF, Roberfroid M (1983) Morphological alterations and DNase deficiency in phenobarbital promotion of N-nitrosomorpholine initiated rat hepatocarcinogenesis. Carcinogenesis 4: 231–234

    Google Scholar 

  77. Sawada N, Furukawa K, Tsukada H (1982) In vitro measurement of resistance to phalloidin and γ-glutamyltransferase of carcinogen-induced preneoplastic hepatocytes of rats. J Natl Cancer Inst 69: 683–686

    Google Scholar 

  78. Denk H Abdelfattah-Gad M, Eckerstorfer R, Talcott RE (1980) Microsomal mixed-function oxidase and activities of some related enzymes in hyperplastic nodules induced by long-term griseofulvin administration in mouse liver. Cancer Res 40: 2568–2573

    Google Scholar 

  79. Feo F, Canuto RA, Garcea R, Brossa O, Caselli GC (1978) Phenobarbital stimulation of cytochrome P-450 and aminopyrine N-demethylase in hyperplastic liver nodules during LD-ethionine carcinogenesis. Cancer Lett 5: 25–30

    Google Scholar 

  80. Farber E (1984) The biochemistry of preneoplastic liver: a common metabolic pattern in hepatocyte nodules. Can J Biochem Cell Biol 62: 486–494

    Google Scholar 

  81. Shinozuka H, Lombardi B, Sell S, Iammarino RM (1978) Early histological and functional alterations of ethionine liver carcinogenesis in rats fed a choline-deficient diet. Cancer Res 38: 1092–1098

    Google Scholar 

  82. Sell S, Leffert HL (1982) An evaluation of cellular lineages in the pathogenesis of experimental hepatocellular carcinoma. Hepatology 2: 77–86

    Google Scholar 

  83. Kunz W, Appel KE, Rickart R, Schwarz M, Stöckle G (1978) Enhancement and inhibition of carcinogenic effectiveness of nitrosamines. In: “Primary Liver Tumors”. (Eds.: Remmer, Bolt, Bannasch and Popper), MTP Press Ltd., International Medical Publishers Lancaster UK pp 261–283

    Google Scholar 

  84. Lans M, de Gerlache J, Taper HS, Preat V, Roberfroid MB (1983) Phenobarbital as a promoter in the initiation/selection process or experimental rat hepatocarcinogenesis. Carcinogenesis 4: 141–144

    Google Scholar 

  85. Pitot HC, Barsness L, Goldsworthy T, Kitagawa T (1978) Biochemical characterisation of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine. Nature 271: 456–458

    Google Scholar 

  86. Moore MA, Hacker HJ, Kunz HW, Bannasch P (1983) Enhancement of NNM-induced carcinogenesis in the rat liver by phenobarbital: a combined morphological and enzyme histochemical approach. Carcinogensis 4: 473–479

    Google Scholar 

  87. Solt D, Farber E (1976) New principle for the analysis of chemical carcinogenesis. Nature 263: 701–703

    Google Scholar 

  88. Shinozuka H, Lombardi B, Abanobi SE (1982) A comparative study of the efficacy of four barbiturates as promoters of the development of γ-glutamyltranspeptidase-psoitive foci in the liver of carcinogen treated rats. Carcinogenesis 3: 1017–1020

    Google Scholar 

  89. Timmermann-Trosiener I, Barthel G, Schulte-Hermann R Growth kinetics of putative preneoplastic foci in rat liver during phenobarbital promotion (in preparation)

  90. Bursch W, Lauer B, Tirnmermann-Trosiener I, Barthel G, Schuppler J, Schulte-Hermann R (1984) Controlled death (Apoptosis) of normal and putative preneoplastic cells in rat liver following withdrawal of tumor promoters. Carcinogenesis 5, 453–458

    Google Scholar 

  91. Stäubli W, Bentley P, Bieri F, Fröhlich E, Waechter F (1984) Inhibitory effect of nafenopin upon the development of diethylnitrosamine-induced enzyme-altered foci within the rat liver. Carcinogenesis 5: 41–47

    Google Scholar 

  92. Deangelo AB, Garrett CT (1983) Inhibition of development of preneoplastic lesions in the livers of rats fed a weakly carcinogenic environmental contaminant. Cancer Lett 20: 199–205

    Google Scholar 

  93. Reddy JK, Lalwai ND (1983) Carcinogenesis by hepatic peroxisome proliferators: Evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. Crit Rev Toxicol 12: 1–58

    Google Scholar 

  94. Reddy JK, Rao, MS (1978) Enhancement by WY-14, 643, a hepatic peroxisome proliferator, of diethylnitrosamine-initiated hepatic tumorigenesis in the rat. Br J Cancer 38: 537–543

    Google Scholar 

  95. Tatematsu M, Nagamine Y, Farber E (1983) Redifferentiation as a basis for remodeling of carcinogen-induced hepatocyte nodules to normal appearing liver. Cancer Res 43: 5049–5058

    Google Scholar 

  96. Moore MA, Hacker H-J, Bannasch P (1983) Phenotypic instability in focal and nodular lesions induced in a short term system in the rat liver. Carcinogenesis 4: 595–603

    Google Scholar 

  97. Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1984) Aberrant expression of adaptation to phenobarbital may cause selective growth of foci of altered cells in rat liver. In: Models, Mechanisms and Etiology of Tumor Promotion. Börzsony, Day (ed) IARC Scientific Publication 56: 67–75

  98. Williams GM, Telang S, Tong C (1981) Inhibition of intercellular communication between liver cells by the liver tumor promoter 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane. Cancer Lett 11: 339–344

    Google Scholar 

  99. Tsushimoto G, Chang CC, Trosko JE, Matsumura F (1983) Cytotoxic, mutagenic, and cell-cell communication inhibitory properties of DDT, Lindane, and chlordane on Chinese hamster cells in vitro. Arch Environ Contam Toxicol 12: 721–730

    Google Scholar 

  100. Kinsella AR (1982) Elimination of metabolic co-operation and the induction of sister chromatid exchanges are not properties common to all promoting or co-carcinogenic agents. Carcinogenesis 3: 499–503

    Google Scholar 

  101. Smith A, Cabral JR (1980) Liver-cell tumors in rats fed hexachlorobenzene. Cancer Lett 11: 169–172

    Google Scholar 

  102. Rossi L, Ravera M, Repetti G, Santi L (1977) Long-term administration of DDT or phenobarbital-Na in wistar rats. Int J Cancer 19: 179–195

    Google Scholar 

  103. Kimbrough RD, Groce DF, Korver MP, Burse VW (1981) Induction of liver tumors in female sherman strain rats by polybrominated piphenyls. J Natl Cancer Inst 66: 535–542

    Google Scholar 

  104. Schuppler J, Schulte-Hermann R, Timmermann-Trosiener I, Günzel P (1982) Proliferative liver lesions and sex steroids in rats. Toxicol Pathol 10: 132–144

    Google Scholar 

  105. Maslandsky CJ, Williams GM (1981) Evidence for an epigenetic mode of action in organochlorine pesticide hepatocarcinogenicity: a lack of genotoxicity in rat, mouse, and hamster hepatocytes. J Toxicol Environ Health 8: 121–130

    Google Scholar 

  106. Planche G, Croisy A, Veille C, Tomatis L, Bartsch H (1979) Metabolic and mutagenicity studies on DDT and 15 derivatives of 1,1-bis(p-chlorophenyl)-2,2-dichloroethane and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethyl acetate (kelthane acetate) as mutagens in salmonella typhimurium and of 1,1-bis(p-chlorophenyl)ethylene oxide, a likely metabolite, as an alkylating agent. Chem-Biol Interact 25: 157–175

    Google Scholar 

  107. Brimfield AA, Street JC (1981) Microsomal activation of chlordane isomers to derivatives that irreversibly interact with cellular macromolecules. J Toxicol Environ Health 7: 193–206

    Google Scholar 

  108. Heine W-D, Stöcker E (1970) Mode of cellular proliferation in the liver of senile rats after partial hepatectomy. Gustav Fischer, Stuttgart Verh Dtsch Ges Path 54: 550–554

    Google Scholar 

  109. Ward JM (1983) Increased susceptibility of livers of aged F344/NCr rats to the effects of phenobarbital on the incidence, morphology, and histochemistry of hepatocellular foci and neoplasms. J Natl Cancer Inst 71: 815–822

    Google Scholar 

  110. Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1983) Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds. Cancer Res 43: 839–844

    Google Scholar 

  111. Peraino C, Staffeldt EF, Ludeman VA (1981) Early appearance of histochemically altered hepatocyte foci and liver tumors in female rats treated with carcinogens one day after birth. Carcinogenesis 2: 463–465

    Google Scholar 

  112. Pereira MA (1982) Rat liver foci bioassay. J Amer Coll Toxicol 1: 101–117

    Google Scholar 

  113. Tatematsu M, Hasegawa R, Imaida K, Tsuda H, Ito N (1983) Survey of various chemicals for initiating and promoting activities in a short-term in vivo system based on generation of hyperplastic liver nodules in rats. Carcinogenesis 4: 381–386

    Google Scholar 

  114. Schuppler J, Damme J, Schulte-Hermann R (1983) Assay of some endogenous and synthetic sex steroids for tumor-initiating activity in rat liver using the Solt-Farber system. Carcinogenesis 4: 239–241

    Google Scholar 

  115. Parzefall W, Galle PR, Schulte-Hermann R: Effect of calf and rat serum on the induction of DNA synthesis and mitosis in primary cultures of adult rat hepatocytes by cyproterone acetate and epidermal growth factor. In Vitro (in press)

  116. Marks F, Fürstenberger G, Kinzel V (1985) A partial inversion of the initiation-promotion approach of skin tumorigensis. J Cancer Res Clin Oncol 109: A16

    Google Scholar 

  117. Kinzel V, Fürstenberger G, Richards J, Loehrke H, Marks F (1985) Studies on the specific promoting capacity of TPA J Cancer Res Clin Oncol 109: A15

    Google Scholar 

  118. Schlicht I, Koransky W, Magour S, Schulte-Hermann R (1968) Größe und DNS-Synthese der Leber unter dem Einfluß körperfremder Stoffe. Naunyn-Schmiedebergs Arch Pharmak exp Path 261: 26–41

    Google Scholar 

  119. Tsuda H, Hasegawa R, Imaida K, Masui T, Moore MA, Jto N (1984) Modifying potential of thirty-one chemicals on the short-term development of γ-glutamyltranspeptidase —posi-tive foci in diethylnitrosamine —initiated rat liver. Gann 75: 876–883

    Google Scholar 

  120. Numoto S, Mori H, Furuya K, Levine WG, Williams GM (1985) Absence of a promoting or sequential syncarcinogenic effect in rat liver by the carcinogenic hypolipidemic drug nefenopin given after N-2-fluorenylacetamide. Toxicol. Appl Pharmacol 77: 76–85

    Google Scholar 

  121. Goldsworhty T, Campbell HA, Pitot HC (1984) The natural history and dose-response characteristics of enzyme-altered foci in rat liver following phenobarbital and diethylnitrosamine administration. Carcinogenesis 5: 67–71

    Google Scholar 

  122. Parzefall W, Schröter C (1985) A dose-response study on the effects of hexachlorocyclohexane isomers on growth, monooxygenases and putative preneoplastic foci in rat liver. Naunyn-Schmiedeberg's Arch Pharmacol Suppl to 329: R 26

  123. Laib RJ, Pellio T, Wünschel UM, Zimmermann N, Bolt HM (1985) The rat liver foci bioassay: II. Investigations on the dose-dependent induction of ATPase-deficient foci by vinyl chloride at very low doses. Carcinogenesis 6: 69–72

    Google Scholar 

  124. Eigenbrodt E, Glossmann H (1980) Glycolysis — one of the keys to cancer? TIPS 240–245

  125. Eigenbrodt E, Fister P, Reinacher M (1985) New perspectives on carbohydrate metabolism in tumor cells. Regulation of carbohydrate metabolism Part II (Beitner R ed) CRC Press, Bocaraton, Florida (in press)

    Google Scholar 

  126. Deml E, Oesterle D (1980) Histochemical demonstration of enhanced glutathione content in enzyme-altered islands induced by carcinogens in rat liver. Cancer Res 40: 490–491

    Google Scholar 

  127. Ochs H, Düsterberg B, Günzel P, Schulte-Hermann R: Effect of tumor promoting contraceptive steroids on growth and drug metabolizing enzymes in rat liver (in press)

  128. Yanagi S, Sakamot M, Ninomiya Y, Kamiya T (1984) Decrease in L-Type pyruvate kinase activity in rat liver by some promoters of hepatocarcinogenesis. J Natl Cancer Inst 73: 887–895

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schulte-Hermann, R. Tumor promotion in the liver. Arch Toxicol 57, 147–158 (1985). https://doi.org/10.1007/BF00290879

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00290879

Keywords

Navigation