Tumour Promotion: Biology and Molecular Mechanisms

  • A. W. Murray
  • A. M. Edwards
  • C. S. T. Hii
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 94 / 2)

Abstract

A promoter can be operationally defined as a compound which enhances the tumour yield in an animal exposed to a low dose of a carcinogen. Promoters act at an early stage in the step-wise induction of malignant cancers, by favouring the cloncal expansion of initiated cells to benign lesions such as papillomas, nodules and polyps. Although mouse skin has been most extensively studied, a number of animal models have been developed in order to study promotion at several other organ sites (Slaga 1983). The restricted aim of this review is to discuss what is known about promotion by some specific agents in two organs (skin and liver) at both the biological and molecular levels. This summary will not be encyclopedic but will attempt to highlight the important unresolved issues. One characteristic of tumour promotion is that there is frequently tissue specificity associated with a particular promoter (see Table 1), and certainly promotion in skin and liver is achieved by different groups of compounds. Consequently, we believe it would also be useful to consider whether the same, different or overlapping mechanisms are involved.

Keywords

Tamoxifen Pyrene Glucagon Plasminogen Calcitonin 

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References

  1. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M (1987) Phorbol ester-inducible genes contain a commoncis element recognised by a TPA-modulated trans-acting factor. Cell 49:729–739PubMedCrossRefGoogle Scholar
  2. Argyris TS (1985) Regeneration and the mechanism of epidermal tumor promotion. CRC Crit Rev Toxicol 14:211–257CrossRefGoogle Scholar
  3. Armato U, Andreis PG, Romano F (1985) The stimulation by the tumor promoters 12-O- tetradecanoylphorbol-13-acetate and phenobarbital of the growth of primary neonatal rat hepatocytes. Carcinogenesis 6:811–821PubMedCrossRefGoogle Scholar
  4. Barbason H, Rassenfosse C, Betz EH (1983) Promotion mechanism of phenobarbital and partial hepatectomy in DNEA hepatocarcinogenesis cell kinetics effect. Br J Cancer 47:517–525PubMedCrossRefGoogle Scholar
  5. Beer DG, Schwarz M, Sawada N, Pitot HC (1986) Expression of H-ras and c-myc protooncogenes in isolated γ-glutamyl transpeptidase-positive rat hepatoeytes and in hepatocellular carcinomas induced by diethylnitrosamine. Cancer Res 46:2435–2441PubMedGoogle Scholar
  6. Berkow RL, Kraft AS (1985) Bryostatin, a non-phorbol macrocyclic lactone, activates intact human polymorphonuclear leukocytes and binds to the phorbol ester receptor. Biochem Biophys Res Commun 131:1109–1116PubMedCrossRefGoogle Scholar
  7. Berridge MJ (1987) Inositol triphosphate and diacylglycerol: two interacting second messengers. Ann Rev Biochem 56:159–193PubMedCrossRefGoogle Scholar
  8. Besterman JM, Duronio V, Cuatrecasas P (1986) Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger. Proc Natl Acad Sci USA 83:6785–6789PubMedCrossRefGoogle Scholar
  9. Betschart JM, Gupta C, Shinozuka H, Virji MA (1987) Modulation of hepatocyte insulin and glucagon receptors in rats fed phenobarbital, a tumor promoter. Proc Am Assoc Cancer Res 28:165Google Scholar
  10. Blumberg PM (1981) In vitro studies on the mode of action of the phorbol esters, potent tumor promoters, part 2. CRC Crit Rev Toxicol 8:199–234CrossRefGoogle Scholar
  11. Blumberg PM, Dunn J A, Jaken S, Jeng AY, Leach KL, Sharkey NA, Yeh E (1984) Specific receptors for phorbol ester tumor promoters and their involvement in biological responses. In: Slaga TJ (ed) Mechanisms of tumor promotion, vol 3. Tumor promotion and carcinogenesis in vitro. CRC Press, Baton Rouge, p 143Google Scholar
  12. Boutwell RK (1964) Some biological aspects of skin carcinogenesis. Prog Exp Tumor Res 4:207–250PubMedGoogle Scholar
  13. Boutwell RK (1974) The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol 2:419–443PubMedCrossRefGoogle Scholar
  14. Boynton AL, Whitfield JF (1980) Stimulation of DNA synthesis in calcium-deprived T51B liver cells by the tumor promoters phenobarbital, saccharin and 12–0- tetradecanoylphorbol-13-acetate. Cancer Res 40:4541–4545PubMedGoogle Scholar
  15. Brandt SJ, Niedel JE, Bell RM, Young WS (1987) Distinct patterns of different protein kinase C mRNAs in rat tissues. Cell 49:57–63PubMedCrossRefGoogle Scholar
  16. Brooks RC, Morell P, DeGeorge J J, McCarthy KD, Lapetina EG (1987) Differential effects of phorbol ester and diacylglycerols on inositol phosphate formation in C62B glioma cells. Biochem Biophys Res Commun 148:701–708PubMedCrossRefGoogle Scholar
  17. Brown K, Quintanilla M, Ramsden M, Kerr IB, Young S, Balmain A (1986) v-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis. Cell 46:447–456PubMedCrossRefGoogle Scholar
  18. Bursch W, Lauer B, Timmermann-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 5:453–458PubMedCrossRefGoogle Scholar
  19. Busser M-T, Lutz WK (1987) Stimulation of DNA synthesis in rat and mouse liver by various tumor promoters. Carcinogenesis 8:1433–1437PubMedCrossRefGoogle Scholar
  20. Carr BI (1987) Pleiotropic drug resistance in hepatoeytes induced by carcinogenes administered to rats. Cancer Res 47:5577–5583PubMedGoogle Scholar
  21. Carter TH (1987) The regulation of gene expression by tumor promoters. In: Barrett JC (ed) Mechanisms of environmental carcinogenesis, vol 1. CRC Press, Baton Rouge, p47Google Scholar
  22. Castagna M (1987) Phorbol esters as signal transducers and tumor promoters. Biol Cell 59:3–13PubMedGoogle Scholar
  23. Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated phospholipid-dependent protein kinase by tumor- promoting phorbol esters. J Biol Chem 257:7847–7851PubMedGoogle Scholar
  24. Chandar N, Amenta J, Kandala JC, Lombardi B (1987) Liver cell turnover in rats fed a choline-devoid diet. Carcinogenesis 8:669–673PubMedCrossRefGoogle Scholar
  25. Crutchley DY, Conan LB, Maynard JR (1980) Induction of plasminogen activator and prostaglandin biosynthesis in HeLa cells by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 40:849–852PubMedGoogle Scholar
  26. de Bustros A, Baylin SB, Berger CL, Roos BA, Leong SS, Nelkin BD (1985) Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma. J Biol Chem 260:98–104PubMedGoogle Scholar
  27. de Gerlache J, Taper HS, Lans M, Preat V, Roberfroid M (1987) Dietary modulation of rat liver carcinogenesis. Carcinogenesis 8:337–340PubMedCrossRefGoogle Scholar
  28. DellaPorta G, Dragani TA, Maneti G (1987) Two-stage liver carcinogenesis in the mouse. Toxicol Pathol 15:229–233CrossRefGoogle Scholar
  29. Diwan BA, Rice JM, Ohshima M, Ward JM, Dove LF (1985) Comparative tumor- promoting activities of phenobarbital, amobarbital, barbital sodium, and barbituric acid on livers and other organs of male F344/NCr rats following initiation with N- nitrosodiethylamine. JNCI 74:509–516PubMedGoogle Scholar
  30. Donnelly TE, Pelling JC, Anderson CL, Dalby D (1987 a) Benzoyl peroxide activation of protein kinase C activity in epidermal cell membranes. Carcinogenesis 8:1871–1874PubMedCrossRefGoogle Scholar
  31. Donnelly TE, Birt DF, Sittler R, Anderson CL, Choe M, Julius A (1987 b) Dietary fat regulation of the association of protein kinase C activity with epidermal cell membranes. Carcinogenesis 8:1867–1870PubMedCrossRefGoogle Scholar
  32. Driedger PE, Blumberg PM (1980) Specific binding of phorbol ester tumor promoters. Proc Natl Acad Sci USA 77:567–571PubMedCrossRefGoogle Scholar
  33. Eckl PM, Whitcomb WR, Meyer SA, Jirtle RL (1987) Effects of phenobarbital and calcium on the growth of normal and preneoplastic hepatocytes. Proc Am Assoc Cancer Res 28:171Google Scholar
  34. Edwards AM, Lucas CM (1985 a) Induction of γ-glutamyl transpeptidase in primary cultures of normal rat hepatocytes by liver tumor promoters and structurally related compounds. Carcinogenesis 6(5):733–739PubMedCrossRefGoogle Scholar
  35. Edwards AM, Lucas CM (1985 b) Phenobarbital and some other liver tumor promoters stimulate DNA synthesis in cultured rat hepatocytes. Biochem Biophys Res Commun 131:103–108PubMedCrossRefGoogle Scholar
  36. Edwards AM, Yusof YAM (1986) Stimulation of hepatocyte DNA synthesis by phorbol esters and mezerein: comparison with effects of xenobiotic liver tumour promoters. Proc Aust Biochem Soc 19:15Google Scholar
  37. Eriksson LC, Blanck A, Bock KW, Mannervik B (1987) Metabolism of xenobiotics in hepatocyte nodules. Toxicol Pathol 15:27–42PubMedCrossRefGoogle Scholar
  38. Farber E (1980) The sequential analysis of liver cancer induction. Biochim Biophys Acta 605:149–166PubMedGoogle Scholar
  39. Farber E (1984) The biochemistry of preneoplastic liver: a common metabolic pattern in hepatocyte nodules. Can J Biochem Cell Biol 62:486–494PubMedCrossRefGoogle Scholar
  40. Farber E, Sarma DSR (1987) Hepatocarcinogenesis: a dynamic cellular perspective. Lab Invest 56:4–22PubMedGoogle Scholar
  41. Fausto N, Thompson NL, Braun L (1987) Purification and culture of oval cells from rat liver. In: Pretlow TG, Pretlow TP (eds) Cell separation. Methods and selected applications. Academic, Orlando, p 45Google Scholar
  42. Fischer G, Ullrich D, Bock KW (1985) Effects of N-nitrosomorpholine and phenobarbital on UDP-glucuronyl-transferase in putative preneoplastic foci of rat liver. Carcinogenesis 6:605–609PubMedCrossRefGoogle Scholar
  43. Fitzer CJ, O’Brian CA, Guillem JG, Weinstein IB (1987) The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several structurally related bile acids. Carcinogenesis 8:217–220PubMedCrossRefGoogle Scholar
  44. Fonne R, Meyer UA (1987) Mechanisms of phenobarbital-type induction of cytochrome P-450 isozymes. Pharmacol Ther 33:19–22PubMedCrossRefGoogle Scholar
  45. Fournier A, Murray AW (1987) Application of phorbol ester to mouse skin causes a rapid and sustained loss of protein kinase C. Nature 330:767–769PubMedCrossRefGoogle Scholar
  46. Fujiki H, Tanaka Y, Miyaka R, Kikkawa U, Nishizuka Y, Sugimura T (1984) Activation of protein kinase C by new classes of tumor promoters; teleocidin and debromaplysiatoxin. Biochem Biophys Res Commun 120:339–343PubMedCrossRefGoogle Scholar
  47. Furstenberger G, Marks F (1983) Growth stimulation and tumor promotion in skin. J Invest Dermatol 81:157s-l61sPubMedCrossRefGoogle Scholar
  48. Furstenberger G, Berry DL, Sorg B, Marks F (1981) Skin tumor promotion by phorbol esters is a two-stage process. Proc Natl Acad Sci USA 78:7722–7726PubMedCrossRefGoogle Scholar
  49. Furstenberger G, Sorg B, Marks F (1983) Tumor promotion by phorbol esters in skin: evidence for a memory effect. Science 220:89–92PubMedCrossRefGoogle Scholar
  50. Gainer HStC, Murray AW (1985) Diacylglycerol inhibits gap junctional communication in cultured epidermal cells: evidence for a role of protein kinase C. Biochem Biophys Res Commun 126:1109–1113PubMedCrossRefGoogle Scholar
  51. Glauert HP, Schwarz M, Pitot HC (1986) The phenotypic stability of altered hepatic foci: effect of the short-term withdrawal of phenobarbital and of the long-term feeding of purified diets after the withdrawal of phenobarbital. Carcinogenesis 7:117–121PubMedCrossRefGoogle Scholar
  52. Goerttler K, Loehrke H, Schweizer J, Hesse B (1979) Systemic two-stage carcinogenesis in the epithelium of the forestomach of mice using 7,12-dimethylbenz(a)anthracene as initiator and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as promoter. Cancer Res 39:1293–1299PubMedGoogle Scholar
  53. Goldsworthy T, Campbell HA, Pitot HC (1984) The natural history and dose response characteristics of enzyme-altered foci in rat liver following phenobarbital and diethyl- nitrosamine administration. Carcinogenesis 5:67–71PubMedCrossRefGoogle Scholar
  54. Goldsworthy TL, Hanigan MH, Pitot HC (1986) Models of hepatocarcinogenesis in the rat-contrasts and comparisons. CRC Grit Rev Toxicol 17:61–89CrossRefGoogle Scholar
  55. Gschwendt M, Horn F, Kittstein W, Furstenberger G, Marks F (1983) Soluble phorbol ester binding sites and phospholipid- and calcium-dependent protein kinase activiy in cytosol of chick oviduct. FEBS Lett 162:147–150PubMedCrossRefGoogle Scholar
  56. Gupta C, Hattori A, Betschart JM, Virji MA, Shinozuka H (1987) Inhibition of EGF binding in rat hepatocytes by liver tumor promoters. Proc Am Assoc Cancer Res 28:113Google Scholar
  57. Hardwick JP, Gonzalez F J, Kasper CB (1983) Transcriptional regulation of rat liver epoxide hydratase, NADPH-cytochrome P-450 oxidoreductase and cytochrome P- 450b genes by phenobarbital. J Biol Chem 258:8081–8085PubMedGoogle Scholar
  58. Hartley J A, Gibson NW, Kilkenny A, Yuspa S (1987) Mouse keratinocytes derived from initiated skin or papillomas are resistant to DNA strand breakage by benzoyl peroxide: a possible mechanism for tumor promotion mediated by benzoyl peroxide. Carcinogenesis 8:1827–1830PubMedCrossRefGoogle Scholar
  59. Hasegawa R, Tsuda H, Shirai T, Kurata Y, Masuda A, Ito N (1986) Effect of timing of partial hepatectomy on the induction of preneoplastic liver foci in rats given hepatocarcinogens. Cancer Lett 32:15–23PubMedCrossRefGoogle Scholar
  60. Hayes MA, Lee G, Tatematsu M, Farber E (1987) Influences of diethylnitrosamine on longevity of surrounding hepatocytes and progression of transplanted persistent nodules during phenobarbital promotion of hepatocarcinogenesis. Int J Cancer 40:58–63PubMedCrossRefGoogle Scholar
  61. Hendrich S, Glauert HP, Pitot HC (1986) The phenotypic stability of altered hepatic foci: effects of withdrawal and subsequent readministration of phenobarbital. Carcinogenesis 7:2041–2045PubMedCrossRefGoogle Scholar
  62. Hendrich S, Campbell HA, Pitot HC (1987) Quantitative stereological evaluation of four histochemical markers of altered foci in multistage hepatocarcinogenesis in the rat. Carcinogenesis 8:1245–1250PubMedCrossRefGoogle Scholar
  63. Hennings H (1987) Tumor promotion and progression in mouse skin. In: Barrett JC (ed) Mechanisms of environmental carcinogenesis, vol 2. CRC Press, Baton Rouge, p 59Google Scholar
  64. Hennings H, Yuspa SH (1985) Two-stage tumor promotion in mouse skin: an alternative interpretation. JNCI 74:735–740PubMedGoogle Scholar
  65. 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 304:67–69PubMedCrossRefGoogle Scholar
  66. Hennings H, Blumberg PM, Pettit GR, Herald CL, Shores R, Yuspa SH (1987 a) Bryostatin 1, an activator of protein kinase C, inhibits tumor promotion by phorbol esters in SENCAR mouse skin. Carcinogenesis 8:1343–1346PubMedCrossRefGoogle Scholar
  67. Hennings H, Michael D, Lichti U, Yuspa SH (1987 b) Response of carcinogen-altered mouse epidermal cells to phorbol esters and calcium. J Invest Dermatol 88:60–65PubMedCrossRefGoogle Scholar
  68. Hiasa Y, Kitahori Y, Ohshima M, Fujita T, Yuasa T, Konishi H, Miyashiro A (1982) Promoting effects of phenobarbital and barbital on development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl)-nitrosamine. Carcinogenesis 3:1187–1190PubMedCrossRefGoogle Scholar
  69. Ho IK, Harris RA (1981) Mechanism of action of barbiturates. Annu Rev Pharmacol Toxicol 21:83–111PubMedCrossRefGoogle Scholar
  70. Huang CL, Ives HE (1987) Growth inhibition by protein kinase C late in mitogenesis. Nature 329:849–850PubMedCrossRefGoogle Scholar
  71. Ito N, Fukushima S, Tsuda H (1984) Carcinogenicity and modification of carcinogenic response by BHA, BHT and other antioxidants. CRC Crit Rev Toxicol 15:109–150CrossRefGoogle Scholar
  72. Jacobs S, Cuatrecasas P (1986) Phosphorylation of receptors for insulin and insulin-like growth factor. 1. Effects of hormones and phorbol esters. J Biol Chem 261:934–939PubMedGoogle Scholar
  73. Jeffrey AM, Liskamp RMJ (1986) Computer-assisted molecular modelling of tumor promoters: rationale for the activity of phorbol esters, teleocidin B, and aplysiatoxin. Proc Natl Acad Sci USA 83:241–245PubMedCrossRefGoogle Scholar
  74. Jones MJ, Murray AW (1986) Effect of membrane perturbation on protein kinase C activation: treatment with exogenous phospholipase C decreases translocation of enzyme to cellular membranes. Biochem Biophys Res Commun 136:1083–1089PubMedCrossRefGoogle Scholar
  75. Kaufmann WK, MacKenzie SA, Rahija RJ, Kaufman DG (1986 a) Quantitative relationship between initiation of hepatocarcinogenesis and induction of altered cell islands. J Cell Biochem 30:1–9PubMedCrossRefGoogle Scholar
  76. Kaufmann WK, Tsao M-S, Novicki DL (1986 b) In vitro colonization ability appears soon after initiation of hepatocarcinogenesis in the rat. Carcinogenesis 7:669–671PubMedCrossRefGoogle Scholar
  77. Kaufmann W, Rahija R, Kaufman D, Goyette M, Dolan M, Shank P, Fausto N (1987) Cellular and genetic alterations during hepatocarcinogenesis in the rat. Fed Proc 46:972Google Scholar
  78. King CS, Cooper J A (1986) Effects of protein kinase C activation after epidermal growth factor binding on epidermal growth factor receptor phosphorylation. J Biol Chem 261:10073–10078PubMedGoogle Scholar
  79. Kinsella AR (1986) Multistage carcinogenesis and the biological effects of tumor promoters. In: Evans FJ (ed) Naturally occurring phorbol esters. CRC Press, Baton Rouge, p 33Google Scholar
  80. Kinzel V, Furstenberger G, Loehrke H, Marks F (1986) Three-stage tumorigenesis in mouse skin: DNA synthesis as a prerequisite for the conversion stage induced by TPA prior to initiation. Carcinogenesis 7:779–782PubMedCrossRefGoogle Scholar
  81. Kitagawa T, Watanabe R, Kayano T, Sugano H (1980) In vitro carcinogenesis of hepatocytes obtained from acetylaminofluorene-treated rat liver and promotion of their growth by phenobarbital. Gann 71:747–754PubMedGoogle Scholar
  82. Klaunig JE, Ruch RJ (1987) Strain and species effects on the inhibition of hepatocyte intercellular communication by liver tumor promoters. Cancer Lett 36:161–168PubMedCrossRefGoogle Scholar
  83. Kleine LP, Whitfield JF, Boynton AL (1986) The glucocorticoid dexamethasone and the tumor promoting artifical sweetener saccharin stimulate protein kinase C from T51B rat liver cells. Biochem Biophys Res Commun 135:33–40PubMedCrossRefGoogle Scholar
  84. Kunz HW, Tennekes HA, Port RE, Schwartz M, Lorke D, Schaude G (1983) Quantitative aspects of chemical carcinogenesis and tumor promotion in liver. Environ Health Perspect 50:113–122PubMedCrossRefGoogle Scholar
  85. Lans M, De Gerlache J, Taper H, Preat V, Roberfroid MB (1983) Phenobarbital as a promoter in the initiation/selection process of experimental rat hepatocarcinogenesis. Carcinogenesis 4:141–144PubMedCrossRefGoogle Scholar
  86. Lechner MC, Sinogas C, Osorio-Almeida ML, Freire MT, Chaumet-Riffaud P, Frain M, Sala-Trepat JM (1987) Phenobarbital-mediated modulation of gene expression in rat liver. Analysis of cDNA clones. Eur J Biochem 163:231–238PubMedCrossRefGoogle Scholar
  87. Loehrke H, Schweizer J, Dederer E, Hesse B, Rosenkranz G, Goerttler K (1983) On the persistence of tumor initiation in two-stage carcinogenesis on mouse skin. Carcinogenesis 4:771–775PubMedCrossRefGoogle Scholar
  88. Loury DJ, Goldsworthy TL, Butterworth BE (1987) The value of measuring cell replication as a predictive index of tissue-specific tumorigenie potential. In: Butterworth BE (ed) Nongenotoxic mechanisms in carcinogenesis. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA, pp 119–136 (Banbury report 25)Google Scholar
  89. Makino T, Obara T, Ura H, Kinugasa T, Kobayashi H, Takahashi S, Konishi Y (1986) Effects of phenobarbital and secondary bile acids on liver, gallbladder and pancreas carcinogenesis initiated by N-nitroso-bis(2-hydroxypropyl)amine in hamsters. JNCI 76:967–975PubMedGoogle Scholar
  90. McGowan J A (1986) Hepatocyte proliferation in culture. In: Guillouzo A, Guguen-Guillouzo C (eds) Research in isolated and cultured hepatocytes. Libbey Eurotext, London, p 14Google Scholar
  91. Mentline R (1986) The tumor promoter 12-O-tetradecanoyl phorbol 13-acetate and regulatory diacylglycerols are substrates for the same carboxylesterase. J Biol Chem 261:7816–7818Google Scholar
  92. Miyaka R, Tanaka Y, Tsuda T, Kaibuchi K, Kikkawa U, Nishizuka Y (1984) Activation of protein kinase C by non-phorbol tumor promoter mezerein. Biochem Biophys Res Commun 121:649–656CrossRefGoogle Scholar
  93. Moore MA, Kitagawa T (1986) Hepatocarcinogenesis in the rat: the effect of promoters and carcinogens in vivo and in vitro. Int Rev Cytol 101:125–173PubMedCrossRefGoogle Scholar
  94. Moore MA, Hacker H-J, Kunz HW, Bannasch P (1983) Enhancement of NNM-induced carcinogenesis in the rat liver by phenobarbital: a combined morphological and enzyme histochemical approach. Carcinogenesis 4:473–479PubMedCrossRefGoogle Scholar
  95. Moore MA, Nakagawa K, Satoh K, Ishikawa T, Sato K (1987) Single GST-P positive liver cells — putative initiated hepatocytes. Carcinogenesis 8:483–486PubMedCrossRefGoogle Scholar
  96. Morin MJ, Kreutter D, Rasmussen H, Sartorelli AC (1987) Disparate effects of activators of protein kinase C on HL-60 promyelocytic leukemia cell differentiation. J Biol Chem 262:11758–11763PubMedGoogle Scholar
  97. Mufson RA, Fischer SM, Verma AK, Gleason GL, Slaga TJ, Boutwell RK (1979) Effects of 12–0-tetradecanoylphorbol-l 3-acetate and mezerein on epidermal ornithine decarboxylase activity, isoproterenol-stimulated levels of cyclic adenosine 3’: 5’- monophosphate, and induction of mouse skin tumors in vivo. Cancer Res 39:1979–1984Google Scholar
  98. Muir JG, Murray AW (1987) Bombesin and phorbol ester stimulate phosphatidylcholine hydrolysis by phospholipase C: evidence for a role of protein kinase C. J Cell Physiol 130:382–391PubMedCrossRefGoogle Scholar
  99. Munir KM, Rao KV, Bhide SV (1984) Effect of hexachlorocyclohexane on diethylnitrosa- mine-induced hepatocarcinogenesis in rat and its failure to promote skin tumors on dimethylbenz(a)anthracene initiation in mouse. Carcinogenesis 5:479–481PubMedCrossRefGoogle Scholar
  100. Murakami K, Chan SY, Routtenberg A (1986) Protein kinase C activation by cis-fatty acid in the absence of Ca2 + and phospholipids. J Biol Chem 261:15424–15429PubMedGoogle Scholar
  101. Murray AW, Fournier A, Hardy SJ (1987) Proteolytic activation of protein kinase C: a physiological reaction? Trend Biochem Sci 12:53–54CrossRefGoogle Scholar
  102. Nakanishi K, Fukushima S, Hagiwara A, Tamamo 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. JNCI 68:497–500PubMedGoogle Scholar
  103. Nims RW, Devor DE, Henneman JR, Lubet RA (1987) Induction of alkoxyresorufm O-dealkylases, epoxide hydrolase and liver weight gain: correlation with liver tumor- promoting potential in a series of barbiturates. Carcinogenesis 8:67–71PubMedCrossRefGoogle Scholar
  104. Nishizuka Y (1986) Studies and perspectives of protein kinase C. Science 233:305–311PubMedCrossRefGoogle Scholar
  105. Ogawa K, Solt DB, Farber E (1980) Phenotypic diversity as an early property of putative preneoplastic hepatocyte populations in liver carcinogenesis. Cancer Res 40:725–733PubMedGoogle Scholar
  106. Ohno S, Kawasaki H, Imajoh S, Inagaki M, Yokokura H, Sakoh T, Hidaka H (1987) Tissue-specific expression of three distinct types of rabbit protein kinase C. Nature 325:161–166PubMedCrossRefGoogle Scholar
  107. Ono Y, Fujii T, Ogita K, Kikkawa U, Igarashi K, Nishizuka Y (1987) Identification of three additional members of rat protein kinase C family: δ-, ε-, and ζ-subspecies. FEBS Lett 226:125–128PubMedCrossRefGoogle Scholar
  108. Pal BC, Topping DC, Griesemer RA, Nelson FP, Nettesheim P (1978) Development of a system for controlled release of benzo(a)pyrene,7,12-dimethylbenz(a)anthracene and phorbol ester for tumor induction in heterotopic tracheal grafts. Cancer Res 38:1376–1383PubMedGoogle Scholar
  109. Pasti G, Lacal JC, Warren BS, Aaronson SA, Blumberg PM (1986) Loss of mouse fibroblast cell response to phorbol esters restored by microinjected protein kinase C. Nature 324:375–377PubMedCrossRefGoogle Scholar
  110. Peraino C, Fry RJ, Staffeldt E (1971) Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorene. Cancer Res 31:1506–1513PubMedGoogle Scholar
  111. Peraino C, Fry RJM, Staffeldt E (1977) Effects of varying the onset and duration of exposure to phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigenesis. Cancer Res 37:3623–3627PubMedGoogle Scholar
  112. Peraino C, Staffeldt EF, Haugen DA, Lombard LS, Stevens FJ, Fry RJM (1980) Effects of varying the dietary concentration of phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigenesis. Cancer Res 40:3268–3273PubMedGoogle Scholar
  113. Peraino C, Richards WL, Stevens FJ (1983) Multistage hepatocarcinogenesis. In: Slaga TJ (ed) Mechanisms of tumor promotion, vol 1. CRC Press, Baton Rouge, p 1Google Scholar
  114. Peraino C, Staffeldt EF, Carnes BA, Ludeman VA, Blomquist JA, Vesselinoviteh SD (1984) Characterization of histochemically detectable altered hepatocyte foci and their relationship to hepatic tumorigenesis in rats treated once with diethylnitrosamine or benzo(a)pyrene within one day after birth. Cancer Res 44:3340–3347PubMedGoogle Scholar
  115. Peraino C, Grdina DJ, Staffeldt EF, Russell JF, Prapuolenis A, Carnes BA (1987) Effects of separate and combined treatments with gamma radiation and diethylnitrosamine in neonatal rats on the induction of altered hepatocyte foci and hepatic tumors. Carcinogenesis 8:599–600PubMedCrossRefGoogle Scholar
  116. Pitot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605:191–215PubMedGoogle Scholar
  117. Pitot HC, Barsness L, Goldsworthy T, Kitagawa T (1978) Biochemical characterisation of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine. Nature 271:456–458PubMedCrossRefGoogle Scholar
  118. 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 40:3616–3620PubMedGoogle Scholar
  119. Pitot HC, Glauert HP, Hanigan M (1985) The significance of selected biochemical markers in the characterization of putative initiated cell populations in rodent liver. Cancer Lett 29:1–14PubMedCrossRefGoogle Scholar
  120. Pitot HC, Goldsworthy TL, Moran S, Kennan W, Glauert HP, Maronpot RR, Campbell HA (1987) A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose-response relationships to altered hepatic foci. Carcinogenesis 8:1491–1499PubMedCrossRefGoogle Scholar
  121. Poland A, Mak I, Glover E (1981) Species differences in the responsiveness to l,4-bis[2- (3,5-dichloropyridyloxy)]-benzene, a potent phenobarbital-like inducer of microsome monooxygenase activity. Mol Pharmacol 20:442–450PubMedGoogle Scholar
  122. Poland A, Palen D, Glover E (1982) Tumor promotion by TCDD in skin of HRS/J hairless mice. Nature 300:271–273PubMedCrossRefGoogle Scholar
  123. Pound AW, McGuire LJ (1978) Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats. Br J Cancer 37:585–594PubMedCrossRefGoogle Scholar
  124. Preat V, Lans M, de Gerlache J, Taper H, Roberfroid M (1987) Influence of the duration and delay of administration of phenobarbital on its modulating effect on rat hepatocarcinogenesis. Carcinogenesis 8:333–335PubMedCrossRefGoogle Scholar
  125. Pugh TD, Goldfarb S (1978) Quantitative histochemical and autoradiographic studies of hepatocarcinogenesis in rats fed 2-acetylaminofluorene followed by phenobarbital. Cancer Res 38:4450–4457PubMedGoogle Scholar
  126. Quintanilla M, Brown K, Ramsden M, Balmain A (1986) Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 322:78–80PubMedCrossRefGoogle Scholar
  127. Rabes HM, Szymkowiak R (1979) Cell kinetics of hepatocytes during the preneoplastic period of diethylnitrosamine-induced liver carcinogenesis. Cancer Res 39:1298–1304PubMedGoogle Scholar
  128. Raik AN, Thum K, Olivers BR (1972) Early effects of 12–0-tetradecanoylphorbol-13- acetate on the incorporation of tritiated precursor into DNA and the thickness of the interfollicular epidermis, and their relation to tumor promotion in mouse skin. Cancer Res 32:1562–1568Google Scholar
  129. Rao MS, Reddy JK (1987) Peroxisome proliferation and hepatocarcinogenesis. Carcinogenesis 8:631–636PubMedCrossRefGoogle Scholar
  130. Reddy BS, Watanabe K (1979) Effects of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germ-free and conventional F344 rats. Cancer Res 39:1521–1524PubMedGoogle Scholar
  131. Roghani M, DaSilva C, Guvelli D, Castagna M (1987 a) Benzene and toluene activate protein kinase C. Carcinogenesis 8:1105–1107PubMedCrossRefGoogle Scholar
  132. Roghani M, DaSilva C, Castagna M (1987 b) Tumour promoter chloroform is a potent protein kinase C activator. Biochem Biophys Res Commun 142:738–744PubMedCrossRefGoogle Scholar
  133. Rotstein J, Sarma DSR, Farber E (1986) Sequential alterations in growth control and cell dynamics of rat hepatocytes in early precancerous steps in hepatocarcinogenesis. Cancer Res 46:2377–2385PubMedGoogle Scholar
  134. Sarma DSR, Rao PM, Rajalakshmi S (1986) Liver tumor promotion by chemicals: models and mechanisms. Cancer Surv 5:781–798PubMedGoogle Scholar
  135. Sawada N, Staecker JL, Pitot HC (1987) Effects of tumor-promoting agents 12-O- tetradecanoylphorbol-13-acetate and phenobarbital on DNA synthesis of rat hepatocytes in primary culture. Cancer Res 47:5665–5671PubMedGoogle Scholar
  136. Schulte-Hermann R (1985) Tumor promotion in the liver. Arch Toxicol 57:147–158PubMedCrossRefGoogle Scholar
  137. 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 41:2556–2562PubMedGoogle Scholar
  138. Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1986) Facilitated expression of adaptive responses to phenobarbital in putative pre-stages of liver cancer. Carcinogenesis 7:1651–1655PubMedCrossRefGoogle Scholar
  139. Schwarz M, Bannasch P, Kunz W (1983) The effect of pre- and post-treatment with phenobarbital on the extent of γ-glutamyl transpeptidase positive foci induced in rat liver by N-nitrosomorpholine. Cancer Lett 21:17–21PubMedCrossRefGoogle Scholar
  140. Sell S, Leffert HL (1982) An evaluation of cellular lineages in the pathogenesis of experimental hepatocellular carcinoma. Hepatology 2:77–86PubMedCrossRefGoogle Scholar
  141. Serra M, Smith TL, Yamamura HI (1986) Phorbol esters alter muscarinic receptor binding and inhibit polyphosphoinositide breakdown in human neuroblastoma (SH-5Y5Y) cells. Biochem Biophys Res Commun 140:160–166PubMedCrossRefGoogle Scholar
  142. Shirai T, Tsuda H, Ogiso T, Hirose M, Ito N (1987) Organ specific modifying potential of ethinyl estradiol on carcinogenesis initiated with different carcinogens. Carcinogenesis 8:115–119PubMedCrossRefGoogle Scholar
  143. Shubik P (1984) Progression and promotion. JNCI 73:1005–1011PubMedGoogle Scholar
  144. Siebert PD, Fukuda M (1985) Regulation of glycophorin gene expression by a tumor promoting phorbol ester in human leukemic K562 cells. J Biol Chem 260:640–645PubMedGoogle Scholar
  145. Sirica AE, Jicinsky JK, Heyer EF (1984) Effect of chronic phenobarbital administration on the gamma-glutamyl transpeptidase activity of hyperplastic liver lesions induced in rats by the Solt/Farber initiation selection process of hepatocarcinogenesis. Carcinogenesis 5:1737–1740PubMedCrossRefGoogle Scholar
  146. Slaga TJ (1983) Mechanisms of tumor promotion, vol 1. Tumor promotion in internal organs. CRC Press, Baton RougeGoogle Scholar
  147. Slaga TJ, Fischer SM, Nelson K, Gleason GL (1980) Studies on the mechanism of skin tumor promotion: evidence for several stages in promotion. Proc Natl Acad Sci USA 77:3659–3663PubMedCrossRefGoogle Scholar
  148. Smith JB, Smith L, Pettit GR (1985) Bryostatins: potent new mitogens that mimic phorbol ester tumor promoters. Biochem Biophys Res Commun 132:939–945PubMedCrossRefGoogle Scholar
  149. Sobczak J, Duguet M (1986) Molecular biology of liver regeneration. Biochimie 68:957–967PubMedCrossRefGoogle Scholar
  150. Taguchi M, Thomas TP, Anderson WB, Farrar WL (1986) Direct phosphorylation of the interleukin 2 receptor TCA antigen epitope by protein kinase C. Biochem Biophys Res Commun 135:239–247PubMedCrossRefGoogle Scholar
  151. Tatematsu M, Hasegawa R, Imaida K, Tsuda H, Ito N (1983 a) Survey of various chemicals from initiating and promoting activities in a short-term in vivo system based on generation of hyperplastic liver nodules in rats. Carcinogenesis 4:381–386PubMedCrossRefGoogle Scholar
  152. Tatematsu M, Nagamine Y, Farber E (1983 b) Redifferentiation as a basis for remodelling of carcinogen-induced hepatocyte nodules to normal appearing liver. Cancer Res 43:5049–5058PubMedGoogle Scholar
  153. Tsuda H, Fukushima S, Imaida K, Kurata Y, Ito N (1983) Organ specific promoting effects of phenobarbital and saccharin in induction of thyroid, liver and urinary bladder tumors in rats after initiation with N-nitrosodiethylurea. Cancer Res 43:3292–3296PubMedGoogle Scholar
  154. Tsuda H, Hasegawa R, Imaida K, Masui T, Moore MA, Ito N (1984) Modifying potential of thirty-one chemicals on the short-term development of γ-glutamyl transpeptidase- positive foci in diethylnitrosamine-initiated rat liver. Gann 75:876–883PubMedGoogle Scholar
  155. Van Duuren BL, Sivak A, Katz C, Siedman I, Melchionne S (1975) The effect of ageing and interval between primary and secondary treatment in two-stage carcinogenesis in mouse skin. Cancer Res 35:502–505PubMedGoogle Scholar
  156. Verma IM, Sassone-Corsi P (1987) Proto-oncogene fos: complex but versatile regulation. Cell 51:513–514PubMedCrossRefGoogle Scholar
  157. Verma AK, Pong RC, Erickson D (1986) Involvement of protein kinase C activation in ornithine decarboxylase gene expression in primary culture of newborn mouse epidermal cells and in skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 46:6149–6155PubMedGoogle Scholar
  158. Weinberg WC, Berkwits L, Iannaccone PM (1987) The clonal nature of carcinogen- induced altered foci of y-glutamyl transpeptidase expression in rat liver. Carcinogenesis 8:565–570PubMedCrossRefGoogle Scholar
  159. Weinstein IB (1987) Growth factors, oncogenes and multistage carcinogenesis. J Cell Biochem 33:213–224PubMedCrossRefGoogle Scholar
  160. Whitlock JP (1987) The regulation of gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Pharmacol Rev 39:147–161PubMedGoogle Scholar
  161. Williams GM, Ohmori T, Katayama S, Rice JM (1980) Alteration by phenobarbital of membrane associated enzymes including gamma-glutamyl transpeptidase in mouse liver neoplasma. Carcinogenesis 1:813–818PubMedCrossRefGoogle Scholar
  162. Yager JD, Roebuck BD, Paluszcyk TL, Memoli VA (1986) Effects of ethinyl estradiol and tamoxifen on liver DNA turnover and new synthesis and appearance of gamma glutamyl transpeptidase-positive foci in female rats. Carcinogenesis 7:2007–2014PubMedCrossRefGoogle Scholar
  163. Yamasaki H, Enomoto T (1985) Role of intercellular communication in BALB/c 3T3 cell transformation. In: Barrett JC, Tennant RW (eds) Carcinogenesis, vol 9. Raven, New York, p 179Google Scholar
  164. Yoshimasa T, Sibley DR, Souvier M, Lefkowitz RJ, Caron MG (1987) Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation. Nature 327:67–70PubMedCrossRefGoogle Scholar
  165. Yuspa SH, Morgan DL (1981) Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature 293:72–74PubMedCrossRefGoogle Scholar
  166. Yuspa SH, Kulesz-Martin M, Ben T, Hennings H (1983) Transformation of epidermal cells in culture. J Invest Dermatol 81:162s–l68sPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • A. W. Murray
  • A. M. Edwards
  • C. S. T. Hii

There are no affiliations available

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