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Cocarcinogens and Cocarcinogenesis (with a note on synergistic processes in carcinogenesis)

  • E. Hecker
Part of the Handbuch der allgemeinen Pathologie book series (PATHOLOGIE, volume 6 / 6)

Abstract

There is a huge number of known carcinogenic factors of assorted origin and nature. These may be divided into solitary carcinogens and cocarcinogens1. From the point of view of environmental hygiene and preventive medicine, solitary carcinogens are carcinogenic factors of “first-order” risk, because chronic exposure to small—or even a single exposure to high—doses of any solitary carcinogen, for example, occupational exposure, may induce neoplasia. Here the toxicologic process is called solitary carcinogenesis. In the majority of cases, neoplasia is probably the result of synergistic action in multifactorial exposures of the host or target tissue to carcinogenic factors, be they solitary carcinogens or cocarcinogens. Here the toxicologic process is called syncarcinogenesis. Exposure of the host or target tissue to cocarcinogens does not per se produce neoplasia. If, however, a submanifestational exposure to a solitary carcinogen is followed by exposure to a cocarcinogen, tumors or cancer will arise. Here the toxicologic process is called cocarcinogenesis. Consequently, in terms of environmental hygiene and preventive medicine, cocarcinogens may be understood to be “second-order” risk factors2.

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References

  1. Adolf, W., Hecker, E.: Further new diterpene esters from the irritant and cocarcinogenic seed oil and latex of the caper spurge (Euphorbia lathyris). Experientia (Basel) 27, 1393–1394 (1971).CrossRefGoogle Scholar
  2. Adolf, W., Hecker, E.: The irritant and cocarcinogenic principles of Hippomane mancinella.Tetrahedron Letters, 1587–1590 (1975).Google Scholar
  3. Arffmann, E., Glavind, J.: Tumor promoting activity of fatty acid methylesters in mice. Experientia (Basel) 27, 1465–1466(1971).CrossRefGoogle Scholar
  4. Armuth, V., Berenblum, I.: Systemic promoting action of phorbol in liver and lung carcinogenesis in AKR mice. Cancer Res. 32, 2259–2262 (1972).PubMedGoogle Scholar
  5. Armuth, V., Berenblum, I.: Promotion of mammary carcinogenesis and leukemogenic action of phorbol in virgin female wistar rats. Cancer Res. 34, 2704–2707 (1974).PubMedGoogle Scholar
  6. Aurelian, L., Royston, I., Davis, H.J.: Antibody to genital herpes simplex virus: Association with cervical atypia and carcinoma in situ. J. nat. Cancer Inst. 45, 455–456 (1970).PubMedGoogle Scholar
  7. Bach, H., Goerttler, K.: Morphologische Untersuchungen zur hyperplasiogenen Wirkung des biologisch aktiven Phorbolesters A1. Virchows Arch. Abt. B. 8, 196–205 (1971).Google Scholar
  8. Baird, W.M., Sedgwick, J.A., Boutwell, R.K.: Effects of phorbol and four diesters of phorbol on the incorporation of tritiated precursors into DNA, RNA and protein in mouse epidermis. Cancer Res. 31, 1434–1439 (1971).PubMedGoogle Scholar
  9. Balmain, A., Hecker, E.: On the biochemical mechanism of tumorigenesis in mouse skin. VI. Early effects of growthstimulating phorbol esters on phosphate transport and phospholipid synthesis in mouse epidermis. Biochim. biophys. Acta (Amst.) 362, 457–468 (1974).CrossRefGoogle Scholar
  10. Berenblum, I.: The cocarcinogenic action of croton resin. Cancer Res. 1, 44–48 (1941a).Google Scholar
  11. Berenblum, I.: The mechanism of carcinogenesis. A. study of significance of cocarcinogenic action and related phenoma. Cancer Res. 1, 807–814 (1941b).Google Scholar
  12. Berenblum, I.: Carcinogenesis as a biological problem. North-Holland Research Monographs Frontier in Biology, vol. 34, edits. A. Neuberger and E.L. Tatum. Amsterdam-Oxford: North-Holland Publ. Company; New York: American Elsevier Publishing Company. Inc. 1974.Google Scholar
  13. Berenblum, I., Lonai, V.: The leukemogenic action of phorbol. Cancer Res. 30, 2744–2748(1970).PubMedGoogle Scholar
  14. Berenblum, I., Shubik, P.: A new quantitative approach to the study of the stages of chemical carcinogenesis in the mouse’s skin. Brit. J. Cancer 1, 383–391 (1947).PubMedCrossRefGoogle Scholar
  15. Bertsch, S., Marks, F.: Lack of an effect of tumor-promoting phorbol esters and of epidermal Gj-chalone on DNA synthesis in the epidermis of newborn mice. Cancer Res. 34, 3283–3288 (1974).PubMedGoogle Scholar
  16. Bingham, E., Horton, A.W.: Environmental carcinogenesis. Experimental observations related to occupational cancer. Advances in biology of skin, vol. VII, Carcinogenesis, p. 183–193. Oxford: Pergamon Press 1966.Google Scholar
  17. Bock, F.G., Burns, R.: Tumor promoting properties of anthralin. J. nat. Cancer Inst. 30, 393–397 (1963).Google Scholar
  18. Boutwell, R.K.: Some biological aspects of skin carcinogenesis. Progr. exp. Tumor Res. 4, 207–250 (1964).Google Scholar
  19. Boutwell, R.K.: The function and mechanism of promoters of carcinogenesis. CRC Crit. Rev. Toxicol. 2,419–443 (1974).PubMedCrossRefGoogle Scholar
  20. Boutwell, R.K., Bosch, D.K.: The tumor-promoting action of phenol and related compounds for mouse skin. Cancer Res. 19, 413–424 (1959).PubMedGoogle Scholar
  21. Butenandt, A.: Biochemische Untersuchungen zum Problem der Krebsentstehung. Verh. dtsch. Ges. inn. Med. (Kongreßbd.) 55, 342–364 (1949).Google Scholar
  22. Clayson, D.B., Pringle, J.A.A.: The influence of a foreign body on the induction of tumors in the bladder epithelium of the mouse. Brit. J. Cancer 20, 564–568 (1966).PubMedCrossRefGoogle Scholar
  23. Coetzer, J., Pieterse, M.J.: The isolation of 12-hydroxydaphnetoxin, a degradation product of a constituent of Lasiosiphon burchelii. J. S. Afr. chem. Inst. 24, 241–243 (1971).Google Scholar
  24. Dontenwill, W.: Erzeugung von Tumoren durch endogen hormonelle Faktoren. Handbuch der experimentellen Pharmakologie, Bd. XVI/13, ed. O. EICHLER, p. 74–199. Berlin-Heidelberg-New York: Springer 1966.Google Scholar
  25. Dontenwill, W., Elmenhorst, H., Harke, H.P., Reckzeh, G., Weber, K.H.: Experimentelle Untersuchungen über die tumorerzeugende Wirkung von Zigarettenrauchkondensaten an der Mäusehaut. III. Untersuchungen zur Identifizierung und Anreicherung tumorauslösender Fraktionen. Z. Krebsforsch. 73, 305–314 (1970).PubMedCrossRefGoogle Scholar
  26. Dowdle, W.R., Nahmias, A.J., Harwell, Pauls, F.P.: Association of antigenic types of herpesvirus hominis with site of viral recovery. J. Immunol. 99, 974 (1967).PubMedGoogle Scholar
  27. Druckrey, H.,Schildbach, A.: Quantitative Untersuchungen zur Bedeutung des Benzpyrens für die carcinogene Wirkung von Tabakrauch. Z. Krebsforsch. 65, 465–470 (1963).CrossRefGoogle Scholar
  28. Evans, F.J., Kinghorn, A.D.: Ingenol fromEuphorbia desmondi. Phytochemistry 13, 1011 (1973).CrossRefGoogle Scholar
  29. Fürstenberger, G., Hecker, E.: Zum Wirkungsmechanismus cocarcinogener Pflanzeninhaltsstoffe. Planta med. (Stuttg.) 22, 241–266 (1972a).Google Scholar
  30. Fürstenberger, G., Henseleit, E., Hecker, E.: Über den Zusammenhang zwischen entzündlicher und cocarcinogener Wirkung von Phorbolderivaten. 11. Wiss. Tag. der Dtsch. Krebsges., Hannover 30.9.-2.10.1971, Inhaltsverzeichnis und Kurzreferate, S. 78 (1972b).Google Scholar
  31. Fusenig, N.E.: Zur Kultivierung von Mäuse-Epidermiszellen in vitro. In: Aktuelle Probleme aus dem Gebiet der Cancerologie (H. Lettre and G. Wagner, eds.), vol. III, p. 83–90 (1971).Google Scholar
  32. Fusenig, N.E., Worst, P.K.M.: Mouse epidermal cell cultures I: Isolation and cultivation of epidermal cells from adult mouse skin. J. invest. Derm. 63, 187–193 (1974).PubMedCrossRefGoogle Scholar
  33. Gericke, D., Kovac, W., Hecker, E.: On a possible cocarcinogenic and immunosuppressive activity of phorbol in AKR mice. Z. Krebsforsch. 82, 183–189 (1974).CrossRefGoogle Scholar
  34. Goerttler, KL., Haag, D., Tasca, C: Cytophotometrische Untersuchungen an Zellkernen von experimentell erzeugten Neoplasmen. Z. Krebsforsch. 76, 155–166 (1971).CrossRefGoogle Scholar
  35. Grimm, W., Marks, F.: Effect of tumor-promoting phorbol esters on the normal and the isoproterenol- elevated level of adenosine 3,5’-cyclic monophosphate in mouse epidermis in vivo. Cancer Res. 34, 3128–3134 (1974).PubMedGoogle Scholar
  36. Gschwendt, M., Hecker, E.: On the biologically active compounds of euphorbiaceae. I. Skin irritant and cocarcinogenic factors from Euphorbia cooperi N.E.Br. Z. Krebsforsch. 80, 335–350 (1973).Google Scholar
  37. Gschwendt, M., Hecker, E.: On the active principles of the spurge family. II. Skin irritant and cocarcinogenic factors from Euphorbia triangularis Desf. Z. Krebsforsch. 81, 193–210 (1974).CrossRefGoogle Scholar
  38. Hecker, E.: Biochemische und molekularbiologische Probleme der Tumorgenese. Z. Arzneimittel-Forsch. (Drug Res.) 18, 978–988 (1968a), see also Grundlagen der Tumorgenese; 2. Deidesheimer Gespräch, Hrsg. Fa. Knoll AG., Ludwigshafen, p. 84–115 (1968a).Google Scholar
  39. Hecker, E.: Cocarcinogenic principles from the seed oil of Croton tiglium and from other euphorbiaceae. Cancer Res. 28, 2338–2349; see also Planta med. (Stuttg.), Suppl. 24–45 (1968b).Google Scholar
  40. Hecker, E.: Isolation and characterization of the cocarcinogenic principles from croton oil. In: Methods in cancer research, herausgeg. von H. B Usch, Bd. VI, p. 439–484. New York-London: Academic Press 1971a.Google Scholar
  41. Hecker, E.: New phorbol esters and related cocarcinogens. Oncology 1970, Proceedings of the X. Internat. Cancer Congr., Houston, Texas, USA, vol. V, p. 213–224. Chicago: Year Book Medical Publishers, Inc. 1971b.Google Scholar
  42. Hecker, E.: Cocarcinogens from euphorbiaceae and thymelaeaceae in pharmacognosy and phytochemistry, edit, by H. Wagner and L. Hörhammer, p. 147–165. Berlin-Heidelberg-New York: Springer 1971c.Google Scholar
  43. Hecker, E.: Aktuelle Probleme der Krebsentstehung. Z. Krebsforsch. 78, 99–122 (1972).CrossRefGoogle Scholar
  44. Hecker, E., Bresch, H.: Incorporation of thymidine, uridine and leucine in the skin of mice after treatment with croton-oil factor Aj (TPA). Proc. Amer. Ass. Cancer Res. 37 (1969).Google Scholar
  45. Hecker, E., Paul, D.: Zum biochemischen Mechanismus der Tumorgenese der Mäusehaut. I. Verteilung und Stoffwechsel intragastral verfütterten 9,10-Dimethyl-(l,2)-benzanthracens in der Maus. Z. Krebsforsch. 71, 153–166 (1968).Google Scholar
  46. Hecker, E., Schmidt, R.: Phorbolesters—the irritants and cocarcinogens of Croton tiglium L. Progr. Chem. Organic Natural Products 31, 377–467 (1974).CrossRefGoogle Scholar
  47. Hergenhahn, M., Kusumoto, W., Hecker, E.: Diterpene esters from “euphorbium” and their irritant and cocarcinogenic activity. Experientia (Basel), 30, 1438–1440 (1974).CrossRefGoogle Scholar
  48. Hergenhahn, M., ADOLF, W., Hecker, E.: Resiniferatoxin and other esters of novel polyfunctional diterpenes from Euphorbia resinifera and unispina. Tetrahedron Letters, 1595–1598 (1975).Google Scholar
  49. Kreibich, G., Hecker, E.: On the active principles of croton oil. X. Preparation of tritium-labelled croton-oil factor A1 and other tritium-labelled phorbol derivatives. Z. Krebsforsch. 74, 448–456 (1970).PubMedCrossRefGoogle Scholar
  50. Kreibich, G., Süss, R., Kinzel, V.: On the biochemical mechanism of tumorigenesis in mouse skin. V. Studies of the metabolism of tumor-promoting and non-promoting phorbol derivatives in vivo and in vitro. Z. Krebsforsch. 81, 135–149 (1974).CrossRefGoogle Scholar
  51. Kreibich, G., Witte, I., Hecker, E.: On the biochemical mechanism of tumorigenesis in mouse skin. IV. Methods for determination of fate and distribution of phorbolester TPA. Z. Krebsforsch. 76, 113–123 (1971).CrossRefGoogle Scholar
  52. Krieg, L., Kühlmann, I., Marks, F.: Effect of tumor-promoting phorbol esters and of acetic acid on mechanisms controlling DNA synthesis and mitosis (chalones) and on the biosynthesis of histidine-rich protein in mouse epidermis. Cancer Res. 34, 3135–3146 (1974).PubMedGoogle Scholar
  53. Kupchan, S.M., Baxter, R.L.: Mezerein: Antileukemic principle isolated from Daphne mecereum L. Science (Washington) 187, 652–653 (1975).CrossRefGoogle Scholar
  54. Kupchan, S.M., Sweeny, J.G., Baxter, R.L., Murae, T., Zimmerly, V.A., Sickles, B.R.: Antileukemic diterpenoid esters from Gnidia lamprantha. J. Amer. chem. Soc. 97, 672–673 (1975).CrossRefGoogle Scholar
  55. Lee, D.J., Wales, J.H., Ayers, J.L., Sinnhuber, O.: Synergism between cyclopropenoid fatty acids and chemical carcinogens in rainbow trout (Salmo gairdneri). Cancer Res. 28, 2312–2318 (1968).PubMedGoogle Scholar
  56. Lee, D.J., Wales, J.H., Sinnhuber, R.O.: Promotion of aflatoxin-induced hepatoma growth in trout by methyl malvalate and sterculate. Cancer Res. 31, 960–963 (1971).PubMedGoogle Scholar
  57. Lewin, L.: Gifte und Vergiftungen, 4. Aufl. des Lehrbuchs der Toxikologie. Berlin: Georg Stilke 1929.Google Scholar
  58. Morton, J.F.: Welensali (Croton flavens): Folk uses and properties. Economic Bot. 25 (4), 457–463 (1971).CrossRefGoogle Scholar
  59. Mottram, J.C.: A developing factor in experimental blastogenesis. J. Path. Bact. 56, 181–187 (1944).CrossRefGoogle Scholar
  60. Münk, K., Ludwig, G.: Properties of plaque variants of herpesvirus hominis strains of genital origin. Arch. ges. Virusforsch. 37, 308–315 (1972).PubMedCrossRefGoogle Scholar
  61. Narisawa, T., Magadia, N.E., Weisburger, J.H., Wynder, E.L.: Promoting effect of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N’-nitro-N-nitrosoguanidine in rats. J. nat. Cancer Inst. 53, 1093–1097 (1974).PubMedGoogle Scholar
  62. Ohigashi, H., Katsumata, H., Kawazu, K., Koshimizu, K., Mitsui, T.: A piscicidal constituent of Excoecaria agallocha. Agricult. biol. Chem. 38, 1093–1095 (1974).CrossRefGoogle Scholar
  63. Ohigashi, H., Kawazu, K., Koshimizu, K., Mitsui, T.: A piscicidal constituent of Sapium japonicum. Agricult. biol. Chem. 36, 2529–2537 (1972).CrossRefGoogle Scholar
  64. Okuda, T., Yoshida, T., Koike, S., Toh, N.: The toxic constituent of the fruits of Aleurites fordii. Chem. pharm. Bull. 22, 971–972 (1974); see also Phytochemistry 14, 509–515 (1975).Google Scholar
  65. Opferkuch, H.J., Hecker, E.: New diterpenoid irritants from Euphorbia ingens. Tetrahedron Letters 261–264 (1974).Google Scholar
  66. Paul, D., Hecker, E.: On the biochemical mechanism of tumorigenesis in mouse skin. II. Early effects on the biosynthesis of nucleic acids induced by initiating doses of DMBA and by promoting doses of phorbol-12,13-diester TPA. Z. Krebsforsch. 73, 149–163 (1969).PubMedCrossRefGoogle Scholar
  67. Penn, I.: Malignant tumors in organ transplant recipients. Ree. Result in Cancer Res., vol. 35. Berlin-Heidelberg-New York: Springer 1970.Google Scholar
  68. Petri, E.: Pathologische Anatomie und Histologie der Vergiftungen. In: Handbuch der speziellen pathologischen Anatomie und Histologie, herausgeg. von F. Henke und O. Labarsch, Bd. 10. Berlin: Springer 1930.Google Scholar
  69. Procter, B.G., Dussalt, P., Rona, G., Chappel, C.I.: Studies on the carcinogenicity of an acetone extract of hashish. Toxicol, appl. Pharmacol. 29, 76 (1974).Google Scholar
  70. Raick, A.N., Thumm, K., Chivers, B.R.: Early effects of 12-O-tetradecanoyl-phorbol-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, 1562–1568 (1972).PubMedGoogle Scholar
  71. Rawls, W.E., Tomplins, F., Figueroa, M.E., Melnick, J.L.: Herpesvirus type 2. Association with carcinoma of the cervix. Science 161, 1255 (1968).PubMedCrossRefGoogle Scholar
  72. Reis, H.E.: Immunosuppression, Tumorentstehung und Tumorwachstum. Z. Krebsforsch. 78, 42–50 (1972).CrossRefGoogle Scholar
  73. Roberts, D.L., Rowland, R.L.: Macrocyclic diterpenes. a-and /M,8,13-Duvatriene-l,3-diols from tobacco. J. Organ. Chem. 27, 3989–3995 (1962).CrossRefGoogle Scholar
  74. Robinson, D.R., West, C.A.: Biosynthesis of cyclic diterpenes in extracts from seedlings of Ricinus communis L. I. Identification of diterpene hydrocarbons formed from mevalonate. Biochemistry 9, 70–79 (1970).PubMedCrossRefGoogle Scholar
  75. Roe, F.J.C., Peirce, W.H.E.: Tumor promotion by citrus oils. Tumors of the skin and urethral orifice in mice. J. nat. Cancer Inst. 24, 1389–1403 (1960).PubMedGoogle Scholar
  76. Roe, F.J.C.: Carcinogenesis and sanity. Fd. Cosmet. Toxicol. 6, 485–489 (1968).CrossRefGoogle Scholar
  77. Roe, F.J.C., Carter, R.L., Mitchley, B.C.V., Peto, R., Hecker, E.: On the persistence of tumor initiation and the acceleration of tumor progression in mouse skin carcinogenesis. Int. J. Cancer 9, 264–273 (1972).PubMedCrossRefGoogle Scholar
  78. Roe, F.J.C., Peirce, W.E.H.: Tumor promotion by Euphorbia latices. Cancer Res. 21, 338–344 (1961).PubMedGoogle Scholar
  79. Roe, F.J.C., Peto, R., Kearns, F., Bishop, D.: The mechanism of carcinogenesis by the neutral fraction of cigarette smoke condensate. Brit. J. Cancer 24, 788–806 (1970).PubMedCrossRefGoogle Scholar
  80. Rohrschneider, L.R., O’brien, D.H., Boutwell, R.K.: The stimulation of phospholipid metabolism in mouse skin following phorbol ester treatment. Biochim. biophys. Acta (Amst.) 280, 57–70 (1972).Google Scholar
  81. RONLAN, A., WICKBERG, B.: The structure of mezerein, a major toxic principle of Daphne mezereum. Tetrahedron Letters 4261–4264 (1970).Google Scholar
  82. Rowland, R.L., Rodgman, A., Schumacher, I.N., Roberts, D.L., Cook, L.C., Walker, W.E., JR.: Macrocyclic diterpene hydroxy esters from tobacco and cigarette smoke. J. Org. Chem. 29, 16–21 (1964).CrossRefGoogle Scholar
  83. Royston, J., Aurelian, L.: Immunofluorescent detection of herpesvirus antigens in exfoliated cells from human cervical carcinoma. Proc. nat. Acad. Sci. (Wash.) 67, 204 (1970).CrossRefGoogle Scholar
  84. Saffiotti, U., Cefis, F., Kolb, L.H.: A method for the experimental induction of bronchiogenic carcinoma. Cancer Res. 28, 104–124(1968).PubMedGoogle Scholar
  85. Saffiotti, U., Shubik, P.: Studies on promoting action in skin carcinogenesis. Nat. Cancer Inst. Monogr. 10, 489–507 (1963).Google Scholar
  86. Sakata, K.: Studies on a piscicidal constituent of Hura crepitans. Part II. Chemical structure of huratoxin. Agricult. biol. Chem. 35, 2113–2126 (1971 a).CrossRefGoogle Scholar
  87. Sakata, K., Kawazu, K., Mitsui, T.: Studies on the piscicidal constituent of Hura crepitans. Part I. Isolation and characterization of huratoxin and its piscicidal activity. Agricult. biol. Chem. 35, 1084–1091 (1971b).CrossRefGoogle Scholar
  88. Sakata, K., Kawazu, K., Mitsui, T., Masaki, N.: Structure and stereochemistry of huratoxin, a piscicidal constituent of Hura crepitans. Tetrahedron Letters 1141–1144 (1971 c).Google Scholar
  89. Samsel, W., Fischer, G., Kovar, R., Fusenig, N.E.: Effects of the tumorpromoting agent 12-O-tetradecanoyl-phorbol-13-acetate on proliferation and differentiation in primary cultures of mouse epidermal cells. Hoppe-Seylers Z. physiol. Chem. 355, 1245–1246 (1974).PubMedGoogle Scholar
  90. Schildknecht, H., Edelmann, G., Maurer, R.: Zur Chemie des Mezereins, des entzündlichen und cocarcinogenen Giftes aus dem Seidelbast Daphne mezereum. Chemiker-Ztg. 94,347–355 (1970).Google Scholar
  91. Schildknecht, H., Maurer, R.: Die Struktur des Mezereins aus der Frucht des Seidelbastes Daphne mezereum. Chemiker-Ztg 94, 849 (1970).Google Scholar
  92. Schmähl, D., Osswald, H.: experimentelle untersuchungen über carcinogene Wirkungen von Krebschemotherapeutica und Immunsuppressiva. Arzneimittel-Forsch. (Drug Research) 20, 1461–1467 (1970).Google Scholar
  93. Schmidt, R.: Structure-activity relationship of substituted benz(a)anthracenes in initiation of mouse skin carcinogenesis in vivo. Second Meeting European Association for Cancer Research, Heidelberg, October 2–5; Abstracts p. 37–38 (1973).Google Scholar
  94. Schmidt, R., Hecker, E.: Untersuchungen über die Beziehungen zwischen Struktur und Wirkung von Phorbolestern. In: Aktuelle Probleme aus dem Gebiet der Cancerologie (H. Lettre and G. Wagner, eds.), vol. III, p. 98–108. Berlin-Heidelberg-New York: Springer 1971.Google Scholar
  95. Setälä, K.: Mechanism of experimental tumorigenesis. XV. Further differences in epidermal response of skin-tumor resistant mice to carcinogen and to tumor enhancer. Europ. J. Cancer 1, 128–146 (1962).Google Scholar
  96. SHEAR, M.J.: Studies on carcinogenesis. V. Methyl derivatives of 1.2-benzanthracene. Amer. J. Cancer 33, 499–537 (1938).Google Scholar
  97. Sinnhuber, O., Lee, D.J., Wales, J.H., Landers, M.K., Keyl, A.C.: Hepatic carcinogenesis of aflatoxin M1 in rainbow trout (Salmo gairdneri) and its enhancement by cyclopropene fatty acids. J. nat. Cancer Inst. 53, 1285–1288 (1974).PubMedGoogle Scholar
  98. Sivak, A., Mossman, B.T., Van Duuren, B.L.: Activation of cell membrane enzymes in the stimulation of cell division. Biochem. biophys. Res. Commun. 46, 605–609 (1972).PubMedCrossRefGoogle Scholar
  99. Stout, G.V., Balkenhol, W.G., Poling, M., Hickernell, G.L.: The isolation and structure of daphnetoxin, the poisonous principles of daphne species. J. Amer. chem. Soc. 92,1070–1071 (1970).CrossRefGoogle Scholar
  100. Süss, R., Kinzel, V.: Phorbolesters as a tool in cell research? Europ. J. Cancer 8, 299–304 (1972).CrossRefGoogle Scholar
  101. Thielmann, H.W., Hecker, E.: Beziehungen zwischen der Struktur von Phorbolderivaten und ihren entzündlichen und tumorpromovierenden Eigenschaften. In: Fortschritte der Krebsforschung, Bd. VII, S. 171–179 (Schmidt, C.G., Wetter, O., Hrsg.). Stuttgart-New York: Schattauer 1969.Google Scholar
  102. Traut, M., Kreibich, G., Hecker, E.: Über die Proteinbindung carcinogener Kohlenwasserstoffe und cocarcinogener Phorbolester. In: Aktuelle Probleme aus dem Gebiet der Cancerologie (H. Lettre and G. Wagner, eds.), vol. III, p. 91–96. Berlin-Heidelberg-New York: Springer 1971.Google Scholar
  103. Tye, R., Stemmer, K.L.: Experimental carcinogenesis of the lung. II. Influence of phenols in the production of carcinoma. J. nat. Cancer Inst. 39, 175–196 (1967).PubMedGoogle Scholar
  104. Uemura, D.: Isolation and structures of irritant substances obtained from Euphorbia species (Euphor- biaceae). Tetrahedron Letters 881–884 (1973).Google Scholar
  105. Uemura, D.: New diterpene 13-oxyingenol derivative isolated from Euphorbia kansui Liou. Tetrahedron Letters 2529–2532 (1974).Google Scholar
  106. Uemura, D., Hirata, Y.: The isolation and structure of two new alkaloides, milliamines A and B, obtained from Euphorbia millii. Tetrahedron Letters 3673–3676 (1971).Google Scholar
  107. Uemura, D., Ohwaki, H., Hirata, Y.: Isolation and structures of 20-deoxy-ingenol, new diterpene derivatives and ingenol derivative obtained from “Kansui”. Tetrahedron Letters 2527–2528 (1974).Google Scholar
  108. Van Duuren, B.L.: Tumor-promoting agents in two-stage carcinogenesis. Progr. exp. Tumor Res. 11, 31–68 (1969).Google Scholar
  109. Van Duuren, B.L., Katz, C., Goldschmidt, B.M.: Cocarcinogenic agents in tobacco carcinogenesis. J. nat. Cancer Inst. 51, 703–705 (1973).PubMedGoogle Scholar
  110. Weissmann, G., Troll, W., Van Duuren, B.L., Sessa, G.: Studies on lysosomes. X. Effects of tumor-promoting agents upon biological and artificial membrane systems. Biochem. Pharmacol. 17,2421–2434(1968).PubMedCrossRefGoogle Scholar
  111. Zechmeister, K., Brandl, F., Hoppe, W., Hecker, E., Opferkuch, H.J., Adolf, W.: Structure determination of the new tetracyclic diterpene ingenol-triacetate with triple product methods. Tetrahedron Letters 4075–4078 (1970).Google Scholar

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© Springer-Verlag Berlin Heidelberg 1975

Authors and Affiliations

  • E. Hecker
    • 1
  1. 1.Deutsches KrebsforchungszentrumInstitut für BiochemieHeidelbergDeutschland

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