Viral-Chemical Combination Effects in Tumorigenesis

  • Yin-tak Woo


Shortly after the discovery of the first tumor virus by Rous (1) in 1911 and the first experimental demonstration of chemical induction of cancer in rabbit skin by painting coal tar by Yamagiwa and Ichikawa (2) in 1915, Rous and Kidd (3, 4) reported that tar enhanced the carcinogenic activity of the Shope papillomavirus for the rabbit skin. Since then, numerous reports of interaction between viruses and chemical carcinogens have been published (revs. 5–15) with the majority of these showing synergism. These findings have attracted increasing attention as evidence is mounting that human populations are often exposed to both viruses and chemical carcinogens and that the high incidence of human cancer in certain geographic areas can be attributed to viral-chemical synergistic action. The focus of this section is to review studies indicative of viral-chemical interaction in tumorigenesis in humans, experimental animals, and cell culture systems.


West Nile Virus Vaccinia Virus Chemical Carcinogen Rabbit Skin Cottontail Rabbit 
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.

Abbreviations Used


aflatoxin B1


adult T-cell leukemia




Burkitt’s lymphoma


bovine papillomavirus


cottontail rabbit papillomavirus




duck hepatitis B virus




Epstein-Barr virus


ground squirrel hepatitis virus


hepatitis B virus


hepatocellular carcinoma




human papillomavirus


human T-cell leukemia virus




murine leukemia virus


nasopharyngeal carcinoma


Shope fibromavirus


Shope papillomavirus,virus




vaccinia virus


woodchuck hepatitis virus


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  1. 1.
    Rous, R.: JAMA 56, 198 (1911).Google Scholar
  2. 2.
    Yamagiwa, K., and Ichikawa, K.: Mitt. Med. Fakult. Kais. Jpn. 15, 295 (1915).Google Scholar
  3. 3.
    Rous, P., and Kidd, J. G.: Science 83, 468 (1936).PubMedCrossRefGoogle Scholar
  4. 4.
    Rous, P., and Kidd, J. G.: J. Exp. Med. 67, 399 (1938).PubMedCrossRefGoogle Scholar
  5. 5.
    Duran-Reynals, F.: Texas Repts. Biol. Med. 15, 306 (1957).Google Scholar
  6. 6.
    Duran-Reynals, M. L.: Prog. Exp. Tumor Res. 3, 148 (1963).PubMedGoogle Scholar
  7. 7.
    Duran-Reynals, M. L.: Acta Unio Intern. Contra Cancrum 19, 792 (1963).Google Scholar
  8. 8.
    Tennant, R. W., and Rascati, R. J.: Mechanisms of Cocarcinogenesis Involving Endogenous Retroviruses. In “Modifiers of Chemical Carcinogenesis” (T. J. Slaga, ed.). Raven Press, New York, 1980, p. 185.Google Scholar
  9. 9.
    Southam, C. M., Tanaka, S., Arata, T., Simkovic, D., Miura, M., and Petropulos, S. F.: Prog. Exp. Tumor Res. 11, 194(1969).PubMedGoogle Scholar
  10. 10.
    Yamamoto, N.: Rev. Physiol. Biochem. Pharmacol. 101, 111 (1984).PubMedCrossRefGoogle Scholar
  11. 11.
    Harris, C. C., and Sun, T.-T.: Cancer Surveys 5, 765 (1986).PubMedGoogle Scholar
  12. 12.
    Henderson, E. E.: J. Natl. Cancer Inst. 80, 476 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    Weinstein, I. B.: Cancer, Detection Prev. 14, 253 (1989).Google Scholar
  14. 14.
    Aboud, M., Rosner, M., Dombrovsky, A., Revazova, T., Feldman, G., Tolpolar, L., Strilitz-Hassan, Y., and Flugel, R. M.: Leukemia Res. 16, 1061 (1992).CrossRefGoogle Scholar
  15. 15.
    Jackson, M. E., Campo, M. S., and Gaukroger, J. M.: Crit. Rev. Oncogenesis 4, 277 (1993).PubMedGoogle Scholar
  16. 16.
    Van Rensburg, S. J., Cook-Mozaffari, P., Van Schalkwyk, D. J., Van der Watt, J. J., Vincent, T. J., and Purchase, I. F.: Br. J. Cancer 51, 713 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    Peers, F., Bosch, X., Kaldor, J., Linsell, A., and Pluijmen, M.: Int. J. Cancer 39, 545 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    Yeh, F. S., Yu, M. C., Mo, C. C., Luo, S., Tong, M. J., and Henderson, B. E.: Cancer Res 49, 2506 (1989).PubMedGoogle Scholar
  19. 19.
    Ross, R. K., Yuan, M. J., Yu, M. C., Wogan, G. N., Qian, G. S., Tu, J. T., Groopman, J. D., Gao, Y. T., and Henderson, B. E.: Lancet 339, 943 (1992).PubMedCrossRefGoogle Scholar
  20. 20.
    Qian, G. S., Ross, R. K., Yu, M. C., Yuan, J. M., Gao, Y. T., Henderson, B. E., Wogan, G. N., and Groopman, J. D.: Cancer Epidemiol. Biomarkers Prev. 3, 3 (1994).PubMedGoogle Scholar
  21. 21.
    Osato, T., Imai, S., Kinoshita, T., Aya, T., Sugiura, M., Koizumi, S., and Mizuno, F.: Epstein-Barr Virus, Burkitt’ Lymphoma, and an African Tumor Promoter. In “Immunobiology and Prophylaxis of Human Herpesvirus Infections” (C. Lopez, ed.). Plenum Press, New York, 1990, p. 147.Google Scholar
  22. 22.
    Ito, Y., Tokuka, H., Ohigashi, H., and Koshimizu, K.: Distribution and Characterization of Environmental Promoter Substances as Assayed by Synergistic Epstein-Barr Virus-Activating System. In “Cellular Interactions by Environmental Tumor Promoters” (H. Fujiki, ed.). Japan Sci. Soc. Press, Tokyo, 1984, p. 125.Google Scholar
  23. 23.
    Ho, J. H. C., Huang, D. P., and Fong, Y. Y.: Lancet ii, 626 (1978).CrossRefGoogle Scholar
  24. 24.
    Chang, K. W., Chang, C. S., Lai, K. S., Chou, M. J., and Choo, K. B.: J. Med. Virol. 28, 57 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    Ito, Y., Matsuda, S., Tokuda, H., and Nakao, Y.: Tumor Promoting Diterpene Esters as Possible Environmental Co-factors of ATL. In “Human T-Cell Leukemia/Lymphoma Virus and Adult T-Cell Leukemia” (R. C. Gallo, M. Essex, and L. Gross, eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1984, p. 69.Google Scholar
  26. 26.
    Lutwick, I. L.: Lancet i, 755 (1979).CrossRefGoogle Scholar
  27. 27.
    Munoz, N. M., and Bosch, F. X.: Epidemiology of Hepatocellular Carcinoma. In “Neoplasms of the Liver” (K. Okuda and K. G. Ishak, eds.). Springer-Verlag, Tokyo, 1987, p. 3.Google Scholar
  28. 28.
    Woo, Y.-t., Lai, D. Y., Arcos, J. C., and Argus, M. F.: “Chemical Induction of Cancer-Structural Bases and Biological Mechanisms,” Vol. IIIC: Natural, Metal, Fiber and Macromolecular Carcinogens. Academic Press, San Diego, 1988.Google Scholar
  29. 29.
    Beasley, R. P.: Cancer 61, 1942 (1988).PubMedCrossRefGoogle Scholar
  30. 30.
    Greenblatt, M. S., Bennett, W. P., Hollstein, M., and Harris, C. C.: Cancer Res. 54, 4855 (1994).PubMedGoogle Scholar
  31. 31.
    Kim, C. M., Koike, K., Saito, I., Miyamura, T., and Jay, G.: Nature 351, 317 (1991).PubMedCrossRefGoogle Scholar
  32. 32.
    Wild, C., Jansen, L. A. M., Cova, L., and Montesano, R.: Environ. Health Perspect. 99, 115 (1993).PubMedCrossRefGoogle Scholar
  33. 33.
    The Gambia Hepatitis Study Group: Lancet i, 1057 (1989).CrossRefGoogle Scholar
  34. 34.
    de Thé, G., Geser, A., and Day, N. E.: Nature 274, 756 (1978).CrossRefGoogle Scholar
  35. 35.
    Shank, R. C.: Epidemiology of Aflatoxin Carcinogenesis. In “Environmental Cancer” (H. F. Kraybill and M. A. Mehlman, eds.). Wiley, New York, 1977, p. 301.Google Scholar
  36. 36.
    Henle, W., Henle, G., and Ho, H. C.: J. Natl. Cancer Inst. 44, 225 (1970).PubMedGoogle Scholar
  37. 37.
    Winkelstein, W.: Am. J. Epidemiol. 131, 945 (1990).PubMedGoogle Scholar
  38. 38.
    Holly, E. A., Whittemore, A. S., Aston, D. A., Ahn, D. K., Nickoloff, B. J., and Kristiansen, J. L.: J. Natl. Cancer Inst. 81, 1726 (1989).PubMedCrossRefGoogle Scholar
  39. 39.
    Cann, A. J., and Chen, I. S. Y.: Human T-Cell Leukemia Virus Types I and II. In “Virology” (B. N. Fields and D. M. Knipe, eds.), 2nd ed. Raven Press, New York, 1990, p. 1501.Google Scholar
  40. 40.
    Dragani, T. A., Manenti, G., Farza, H., Delia Porta, G., Tiollais, P., and Pourcel, C.: Carcinogenesis 11, 953 (1989).CrossRefGoogle Scholar
  41. 41.
    Sell, S., Hunt, J. M., Dunsford, H. A., and Chisari, F. V.: Cancer Res. 51, 1278 (1991).PubMedGoogle Scholar
  42. 42.
    Rous, P., and Friedewald, W. F.: J. Exp. Med. 79, 511 (1944).PubMedCrossRefGoogle Scholar
  43. 43.
    Rogers, S., and Rous, P.: J. Exp. Med. 93, 459 (1951).PubMedCrossRefGoogle Scholar
  44. 44.
    Jarrett, W. F. H.: Bull. Cancer 65, 191 (1978).PubMedGoogle Scholar
  45. 45.
    Campo, M. S., Moar, M. H., Jarrett, W. F. H., and Laird, H. M.: Nature 286, 180 (1980).CrossRefGoogle Scholar
  46. 46.
    Campo, M. S.: Cancer Surveys 6, 39 (1987).PubMedGoogle Scholar
  47. 47.
    Rowson, K. E. K., Roe, F. J. C., Ball, J. K., and Salaman, M. H.: Nature 191, 893 (1961).PubMedCrossRefGoogle Scholar
  48. 48.
    Roe, F. J. C., and Rowson, K. E. K.: Int. Rev. Exp. Pathol. 6, 181 (1968).PubMedGoogle Scholar
  49. 49.
    Ahlström, C. G., and Andrewes, C. N.: J. Pathol. Bacteriol. 47, 65 (1938).CrossRefGoogle Scholar
  50. 50.
    Carr, J. G.: Br. J. Exp. Pathol. 23, 221 (1942).Google Scholar
  51. 51.
    Irons, R. D.: Environ. Health Perspect. 86, 49 (1990).PubMedCrossRefGoogle Scholar
  52. 52.
    Tanaka, S., and Southam, C. M.: J. Natl. Cancer Inst. 34, 441 (1965).PubMedGoogle Scholar
  53. 53.
    Imagawa, D. T., Yorhimori, M., and Adams, J. M.: Proc. Am. Assoc. Cancer Res. 2, 217 (1957).Google Scholar
  54. 54.
    Kotin, P., and Wiseley, D. V.: Prog. Exp. Tumor Res. 3, 186 (1963).PubMedGoogle Scholar
  55. 55.
    Harris, R. J., and Negroni, C.: Br. Med. J. 58, 6337 (1967).Google Scholar
  56. 56.
    Schmidt-Ruppin, K. H., and Papadopulu, G.: Z. Krebsforsch. 77, 150 (1972).CrossRefGoogle Scholar
  57. 57.
    Sherker, A. H., and Marion, P.: Annu. Rev. Microbiol. 45, 475 (1991).PubMedCrossRefGoogle Scholar
  58. 58.
    Rogler, C. E.: Curr. Top. Microbiol. Immunobiol. 168, 104 (1991).Google Scholar
  59. 59.
    Cova, L., Duflot, A., Prave, M., and Trepo, C.: Arch. Virol. [Suppl.] 8, 81 (1993).Google Scholar
  60. 60.
    Shope, R. E., and Hurst, E. W.: J. Exp. Med. 58, 607 (1933).PubMedCrossRefGoogle Scholar
  61. 61.
    Lancaster, W. D., and Olson, C.: Microbiol. Rev. 46, 191 (1982).PubMedGoogle Scholar
  62. 62.
    Syverton, J. T.: Ann. NY Acad. Sci. 54, 1126 (1952).PubMedCrossRefGoogle Scholar
  63. 63.
    Shope, R. E.: J. Exp. Med. 56, 803 (1932).PubMedCrossRefGoogle Scholar
  64. 64.
    Andrewes, C., Allison, A. C., Armstrong, J. A., Bearcroft, G., Niven, J. S. F., and Pereira, H. S.: Acta Unio Int. Contra Cancrum 15, 760 (1959).PubMedGoogle Scholar
  65. 65.
    Bearcroft, W. G. C., and Jamieson, M. F.: Nature 182, 195 (1958).PubMedCrossRefGoogle Scholar
  66. 66.
    LaPlaca, M., Portolani, M., Mannini-Palenzona, A., Barbanti-Brodano, G., and Bernardini, A.: J. Microbiol. 15, 205 (1967).Google Scholar
  67. 67.
    Vreeswijk, J., Leene, W., and Kalsbeek, G. L.: J. Invest. Dermatol. 69, 249 (1977).PubMedCrossRefGoogle Scholar
  68. 68.
    Pound, A. W., and Withers, H. R.: Br. J. Cancer 17, 460 (1963).PubMedCrossRefGoogle Scholar
  69. 69.
    Rous, P., and Kidd, J. G.: J. Exp. Med. 73, 365 (1941).PubMedCrossRefGoogle Scholar
  70. 70.
    Deelman, H. T.: Z. Krebsforsch. 18, 261 (1923).Google Scholar
  71. 71.
    Pullinger, B. D.: J. Pathol. Bacteriol. 57, 477 (1945).PubMedCrossRefGoogle Scholar
  72. 72.
    Salaman, M. H., and Glendenning, O. M.: Br. J. Cancer 11, 434 (1957).PubMedCrossRefGoogle Scholar
  73. 73.
    Mazurenko, N. P.: Probl. Oncol. (USSR). (English Transl.) 6, 873 (1960).Google Scholar
  74. 74.
    Sula, J.: Neoplasma 26, 1 (1979).Google Scholar
  75. 75.
    Askanazy, M.: Zentrabl. allg. Pathol, pathol. Anat. 30, 443 (1919).Google Scholar
  76. 76.
    Tsang, S. S., and Stich, H. F.: Cancer Lett. 43, 93 (1988).PubMedCrossRefGoogle Scholar
  77. 77.
    Pennie, W. D., and Campo, M. S.: Virology 190, 861 (1992).PubMedCrossRefGoogle Scholar
  78. 78.
    Mitrani-Rosenbaum, S., and Tsvieli, R.: Intervirology 33, 76 (1992).PubMedGoogle Scholar
  79. 79.
    Garrett, L. R., Perez-Reyes, N., Smith, P. P., and McDougall, J. K.: Carcinogenesis 14, 329 (1993).PubMedCrossRefGoogle Scholar
  80. 80.
    Self, R.: J. Virol. 36, 421 (1980).Google Scholar
  81. 81.
    Diamond, L., Knorr, R., and Shimizu, Y.: Cancer Res. 34, 2599 (1974).PubMedGoogle Scholar
  82. 82.
    Reznikoff, C. A., Loretz, L. J., Christian, B. J., Wu, S.-Q., and Meisner, L. F.: Carcinogenesis 9, 1427 (1988).PubMedCrossRefGoogle Scholar
  83. 83.
    Martin, R. G., Stelow, V. P., and Edwards, C. A. F.: Virol. 31, 596 (1979).Google Scholar
  84. 84.
    Tomei, L. D., Noyes, I., Blocker, D., Holliday, J., and Glaser, R.: Nature 329, 73 (1987).PubMedCrossRefGoogle Scholar
  85. 85.
    Yamamoto, N., and zur Hausen, H.: Nature 280, 244 (1979).PubMedCrossRefGoogle Scholar
  86. 86.
    Casto, B. C.: Cancer Res. 33, 402 (1973).PubMedGoogle Scholar
  87. 87.
    Casto, B. C., Pieczynski, W. J., and DiPaolo, J. A.: Cancer Res. 34, 72 (1974).PubMedGoogle Scholar
  88. 88.
    Casto, B. C., Meyer, J., and DiPaolo, J. A.: Cancer Res. 39, 193 (1979).PubMedGoogle Scholar
  89. 89.
    Fisher, P. B., Weinstein, I. B., Eisenberg, D., and Ginsberg, H.: Proc. Natl. Acad. Sci. U.S.A. 75, 2311 (1978).PubMedCrossRefGoogle Scholar
  90. 90.
    Fisher, P. B., Mufson, R. A., Weinstein, I. B., and Little, J. B.: Carcinogenesis 2, 183 (1981).PubMedCrossRefGoogle Scholar
  91. 91.
    Freeman, A. E., Price, P. J., Igel, H. J., Young, J. C., Maryak, J. M., and Huebner, R. J.: J. Natl. Cancer Inst. 44, 65 (1970).PubMedGoogle Scholar
  92. 92.
    Lipp, M., Scherer, B., Lips, G., Brandner, G., and Hunsmann, G.: Carcinogenesis 3, 261 (1982).PubMedCrossRefGoogle Scholar
  93. 93.
    Rhim, J. S., Vass, W., Cho, H. Y., and Huebner, R. J.: Int. J. Cancer 7, 65 (1971).PubMedCrossRefGoogle Scholar
  94. 94.
    Howard, D. K., Schlom, J. H., and Fisher, P. B.: In Vitro 19, 58 (1983).PubMedCrossRefGoogle Scholar
  95. 95.
    Matsuda, S., Nakao, Y., Ohigashi, H., Koshimizu, K., and Ito, Y.: Int. J. Cancer 38, 859 (1986).PubMedCrossRefGoogle Scholar
  96. 96.
    Frolov, A. F., Sherbinskaya, A. M., and Botsman, N. E.: Folia Biol. 17, 521 (1971).Google Scholar
  97. 97.
    zur Hausen, H., Yamamoto, N., and Bauer, G.: Virus Induction by Tumor Promoters. In “Carcinogenesis”, Vol. 7 (E. Hecker, ed.). Raven Press, New York, 1982, p. 617.Google Scholar
  98. 98.
    Yamamoto, N.: Rev. Physiol. Biochem. Pharmacol. 101, 111 (1984).PubMedCrossRefGoogle Scholar
  99. 99.
    Hashida, T., and Yamamoto, S.: J. Gen. Virol. 72, 1569 (1991).PubMedCrossRefGoogle Scholar
  100. 100.
    Ishidate, M.: “Data Book on Chromosome Aberration Tests in vitro”. Elsevier, Amsterdam, 1988.Google Scholar

Copyright information

© Birkhäuser Boston 1995

Authors and Affiliations

  • Yin-tak Woo
    • 1
  1. 1.Tulane University School of MedicineNew OrleansUSA

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