Cocarcinogens of the Diterpene Ester Type as Principal Risk Factors of Cancer in Curaçao and Possibly in South China:

Identification of Second Order Risk Factors of Cancer in Multifactorial Carcinogenesis
  • E. Hecker


Besides curing diseases of all kinds, traditionally the old culture of China has also been committed to the idea of prevention of diseases, as reflected in the Chinese saying: “Treat a person before he has fallen ill and not only when he is already sick” [50]. Indeed, major aspects of research pursued in my laboratory group at the German Cancer Research Center are guided by the idea of contributing to the prevention of cancer by the identification of the risk factors involved, especially of cocarcinogens of the promotor type. Another important aspect is the investigation of the biochemical mechanism of action of such risk factors to provide clues for their chemical redesign to medicinally useful anticancer drugs.


Esophageal Cancer Raji Cell Minimal Content NMRI Mouse Early Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adolf W, Chanai S, Hecker E: 3-0-Angeloylingenol, the toxic and skin irritant factor from latex of Euphorbia antiquorum L. (Euphorbiaceae) and from a derived Thai purgative and anthelmintic (vermifuge) drug. J. Sci. Soc. Thailand 9 (1983) 81–88CrossRefGoogle Scholar
  2. 2.
    Adolf W, Opferkuch HJ, Hecker E: Irritant phorbol derivatives from four Jatropha species (Euphorbiaceae). Phytochemistry 23 (1984) 129–132CrossRefGoogle Scholar
  3. 3.
    Albert RE: Carcinogen policy at EPA. Science 219 (1983) 796–798PubMedCrossRefGoogle Scholar
  4. 4.
    Ames BN: Dietary carcinogens and anticarcinogens — oxygen radicals and degenerative diseases. Science 221 (1983) 1256–1264PubMedCrossRefGoogle Scholar
  5. 5.
    Amtmann E, Sauer G, Volm M et al: Synergism between latent papillomavirus genomes and a tumor promoter in the rodent Mastomys natalensis. In Abstracts of the International Symposium of the Role of Co-carcinogens and Promoters in Human and Experimental Carcinogenesis, Budapest, May 16–8, 1983, p. l.Google Scholar
  6. 6.
    Benbrook CM: Carcinogen policy at EPA. (Letter). Science 219 (1983) 798PubMedCrossRefGoogle Scholar
  7. 7.
    de Boer SY: Frequentia van Kanker van Mond-Tong-Pharynx-Slokdarm en de Nederlandse Antillen. Diss. Landslaboratorium voor de Volkszondheit, Afdeling Pathologisch Anatomisches Laboratorium Curaçao, Niederländische Antillen, 1979Google Scholar
  8. 8.
    Bohrmann JS: Identification and assessment of tumor-promoting and cocarcinogenic agents: state-of-art in vitro methods. Critic. Rev. Toxicol. 11 (1983) 131–167Google Scholar
  9. 9.
    Cheng JS, Sala M, Li MH et al: Esophageal cancer in Linxian County, China: A possible etiology and mechanism (initiation and promotion). In E Hecker, NE Fusenig, W Kunz et al (Eds): Carcinogenesis, Vol.7: Cocarcinogenesis and Biological Effects of Tumor Promoters, pp 167–174, New York: Raven Press 1982Google Scholar
  10. 10.
    Dunham LJ, Bailar JC: World maps of cancer mortality rates and frequency ratios. J. nat. Cancer Inst. 41 (1968) 155–203PubMedGoogle Scholar
  11. 11.
    Eps LW: Esophageal cancer. Paper of Post Graduate Course 1970 Medical Library of the St. Elizabeth Hospital, Curaçao, 1970Google Scholar
  12. 12.
    Gissman L: Papilloma viruses and their association with cancer in animals and in man. Cancer Surv. 3 (1984) 161–181Google Scholar
  13. 13.
    Hecker E: Aktuelle Probleme der Krebsentstehung. Z. Krebsforsch. 78 (1972) 99–122CrossRefGoogle Scholar
  14. 14.
    Hecker E: Definitions and terminology in cancer (tumor) etiology — an analysis aiming at proposals for a current internationally standardized terminology, a) Int. J. Cancer 18 (1976) 122–129. b)Z. Krebsforsch. 86 (1976) 219–230. c)Gann67 (1976) 471–481. d) Bull. Wrld Hlth Org. 54 (1976) 1–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Hecker E: Structure-activity relationships in diterpene esters irritant and cocarcinogenic to mouse skin. In TJ Slaga, A Sivak, RK Boutwell (Eds): Carcinogenesis, Vol.2: Mechanisms of Tumor Promotion and Cocarcinogenesis, pp 11–48. New York: Raven PressGoogle Scholar
  16. 16.
    Hecker E: Diterpene ester type modulators of carcinogenesis — new findings in the mechanisms of chemical carcinogenesis and the etiology of human tumors. In E. C. Miller, J. A. Miller, T. Horono et al (Eds): Naturally Occurring Carcinogens — Mutagens and Modulators of Carcinogenesis, pp 263–286. Tokyo: Japan Sci. Soc. Press 1979Google Scholar
  17. 17.
    Hecker E: Co-carcinogenesis and tumor promoters of the diterpene ester type as possible carcinogenic risk factors. J. Cancer Res. clin. Oncol. 99 (1981) 103–124PubMedCrossRefGoogle Scholar
  18. 18.
    HeckerE: Prototype processes as experimental models in multifactorial carcinogenesis. J. Cancer Res. clin. Oncol. 99 (1981) A29CrossRefGoogle Scholar
  19. 19.
    Hecker E: Co-carcinogens of the tumor promoter type as potential risk factors of cancer in man — a first complete experimental analysis of an etiological model situation and some of its consequences. In M. Börszönyi, N. E. Day, K. Lapis et al (Eds): Models, Mechanisms and Etiology of Tumour Promotion, pp 441–446. Lyon: IARC 1984. ( IARC Sci. Publ. No. 56 )Google Scholar
  20. 20.
    Hecker E: Concluding remarks and future perspectives. In M. Börszönyi, N. E. Day, K Lapis et al (Eds): Models, Mechanisms and Etiology of Tumour Promotion, pp 509–521. Lyon: IARC 1984. ( IARC Sci. Publ. No. 56 )Google Scholar
  21. 21.
    Hecker E: Cocarcinogens of the initiation(or-tumor)-promoter type as environmental risk factors of cancer in man — experimental analysis of an etiologic model situation of life style cancer and current problems of assessment of cancer risk in multifactorial carcinogenesis. Acta Pharmacol. Toxicol. 55, Suppl. 2 (1984) 145–164CrossRefGoogle Scholar
  22. 22.
    Hecker E: Multifaktorielle und Mehrstufen-Karzinogenese — ätiologische (epidemiologische) und experimentelle Modelle sowie aktuelle Probleme der Bewertung von Krebsrisikofaktoren der Umwelt. In K. E. Appel, A. G. Hildebrandt (Hrsg.): Tumorpromotoren — Erkennung, Wirkungsmechanismen und Bedeutung, S. 14–42. München: MMV Medizin Verlag 1985. ( BGA-Schriften Nr. 6 )Google Scholar
  23. 23.
    Hecker E, Fusenig NE, Kunz W et al (Eds): Carcinogenesis — A Comprehensive Survey. Vol. 7: Cocarcinogenesis and Biological Effects of Tumor Promoters. New York: Raven Press 1982.Google Scholar
  24. 24.
    Hecker E, Lutz D, Weber J et al: Multistage tumor development in the human esophagus — the first identification of cocarcinogens of the tumor promoter type as principal carcinogenic risk factors in a local life style cancer. In 13th International Cancer Congress, Part B. Biology of Cancer (1), pp 219–238. New York: A. R. Liss 1983Google Scholar
  25. 25.
    Hecker E, Weber J: Cocarcinogens from Croton flavens L. and the high incidence of esophageal cancer in Curaçao. In Abstracts of the 7th International Symposium on the Biological Characterization of Human Tumors, Budapest, April 13–15,1977, p 52; Experientia 34 (1978) 679–682PubMedCrossRefGoogle Scholar
  26. 26.
    Higginson J: A global perspective of environmental carcinogenesis. In P Emmlot, E Kriek (Eds): Environmental Carcinogenesis, pp 9–22. Amsterdam: Elsevier/North-Holland 1979.Google Scholar
  27. 27.
    Hirayama T: Operational epidemiology of cancer. J. Cancer Res. clin. Oncol. 99 (1981) 15–28PubMedCrossRefGoogle Scholar
  28. 28.
    Hirayama T, Ito Y: A new view of the etology of nasopharyngeal carcinoma. Prev. Med. 10 (1981) 614–622PubMedCrossRefGoogle Scholar
  29. 29.
    IARC: Approaches to Classifying Chemical Carcinogens According to Mechanism of Action. IARC Techn. Rep. No. 83 /001, 1983Google Scholar
  30. 30.
    IARC: Proceedings. Symposium on the Role of Co-carcinogens and Promoters in Human and Environmental Carcinogenesis. Lyon: IARC 1984. (IARC Sei. Publ. No. 56 )Google Scholar
  31. 31.
    Ito Y, Ohigashi H, Koshimizu K et al: Epstein-Barr-virus-activating principle in the ether extracts of soils collected from under plants which contain active diterpene esters. Cancer Lett. 19 (1983) 113–117PubMedCrossRefGoogle Scholar
  32. 32.
    Ito Y, Yamase S, Tokuda H et al: Epstein-Barr virus activation by tung oil, extracts of Aleurides fordiiand its diterpene ester 12-0-hexadecanoyl-16-hydroxyphorbol-13-acetate. Cancer Lett. 18 (1983) 87–95PubMedCrossRefGoogle Scholar
  33. 33.
    Kunz HW, Schwarz M, Tennekes H et al: Dose/time response characteristics of chemical carcinogenesis and tumor promotion in liver. Proceedings. Symposium on the Role of Co-carcinogens and Promoters in Human and Experimental Carcinogenesis, May 16–18, 1983, Budapest, HungaryGoogle Scholar
  34. 34.
    Lutz D, Hecker E: Esophageal cancer on Curaçao — further new tumor promoters from Croton flavens L. Book of Abstracts. 8th International Symposium on the Biological Characterization of Human Tumors. May 8–11,1979, Athens, GreeceGoogle Scholar
  35. 35.
    Marshall E: EPA’s high risk carcinogen policy. Science 218 (1982) 975–978PubMedCrossRefGoogle Scholar
  36. 36.
    Morton JF: A survey of medicinal plants of Curaçao. Econ. Bot. 22 (1968) 87–102CrossRefGoogle Scholar
  37. 37.
    Morton JF: Plants associated with esophageal cancer cases in Curaçao. Cancer Res. 28 (1968) 2268–2271PubMedGoogle Scholar
  38. 38.
    Morton JF: Folk remedy plants and esophageal cancer in Coro, Venezuela. Morris Arboretum Bull. 25 (1974) 24–34Google Scholar
  39. 39.
    Morton JF: Plant tannins and esophageal cancer. Proc. 10th International Conference on Toxicology and Occupational Medicine, pp 129–137. Amsterdam: Elsevier/North- Holand 1979Google Scholar
  40. 40.
    Takada K, zur Hausen H: Induction of Epstein-Barr virus antigens by tumor promoters for epidermal and non-epidermal tissues. Int. J. Cancer 33 (1984) 491–496PubMedCrossRefGoogle Scholar
  41. 41.
    Tuyns AJ, Pequignot G, Abbalucci JS: Oesophageal cancer and alcohol consumption: Importance of type of beverage. Int. J. Cancer 23 (1979) 443–447PubMedCrossRefGoogle Scholar
  42. 42.
    Todhunter JA: Carcinogen policy at EPA. (Letter). Science 219 (1983) 794Google Scholar
  43. 43.
    Waterhouse J, Muir C, Correa P et al (Eds): Cancer Incidence in Five Continents. Vol. III. Lyon: IARC 1976. (IARC Sci. Publ, No. 15 )Google Scholar
  44. 44.
    Weinstein IB: Carcinogen policy at EPA. (Letter). Science 219 (1983) 794–796CrossRefGoogle Scholar
  45. 45.
    Wynder EL, Hoffmann DH: Tobacco and health: A societal challenge. New Engl. J Med. 300 (1979) 894–903PubMedCrossRefGoogle Scholar
  46. 46.
    Wynder EL, Hultberg S, Jacobson F et al: Environmental factors in cancer of the upper alimentary tract. Cancer 10 (1957) 470–487PubMedCrossRefGoogle Scholar
  47. 47.
    Yamamoto H, Katsuki T, Hinoma Y et al.: Induction of Epstein-Barr virus by a new tumor promoter teleocidin, compared to induction by TP A. Int. J. Cancer 28 (1981) 125–129PubMedCrossRefGoogle Scholar
  48. 48.
    Yamamoto N: Interaction of viruses with tumor promoters. Rev. Physiol. Biochem. Phar-macol. 101 (1984) 111–159CrossRefGoogle Scholar
  49. 49.
    Zeng Y, Zhong JM, Mo YK et al: Epstein-Barr virus early antigen induction in Raji cells by Chinese medicinal herbs. Intervirology 19 (1983) 201–204PubMedCrossRefGoogle Scholar
  50. 50.
    Zhong SZ: Ancient China’s Scientists. Hongkong: Commercial Press 1984Google Scholar
  51. 51.
    Zur Hausen H, O’Neill FB, Freese UK et al: Persisting oncogenic herpesvirus induced by the tumor promoter TPA. Nature 272 (1978) 373–374PubMedCrossRefGoogle Scholar
  52. 52.
    Zur Hausen H, Bornkamm GW, Schmidt R et al: Tumor initiators and promoters in the induction of Epstein-Barr virus. Proc. nat. Acad. Sci. 76 (1979) 782–785CrossRefGoogle Scholar
  53. 53.
    Zur Hausen H, Schulte-Holthausen H, Klein G et al: EBV DNA in biopsies of Burkitt tumors and anaplastic carcinomas of the nasopharynx. Nature 228 (1979) 1076Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • E. Hecker

There are no affiliations available

Personalised recommendations