Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Fifty years of benzo(a)pyrene

It is fifty years since the publication of the report on the isolation, from coal tar, and identification of the potent chemical carcinogen benzo(a)pyrene, the culmination of over 10 years of research instigated and directed by E.L. Kennaway. The events leading to that discovery are of interest in themselves. Subsequent progress in unravelling the metabolic fate of polycyclic aromatic hydrocarbons has contributed to our understanding of the mechanism of chemical carcinogenesis.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

References

  1. Volkmann, R. Beiträge Zur Chirurgie (Breitkopf und Hartel, Leipzig, 1875).

    Google Scholar 

  2. Bell, J. Edinb. med. J. 22, 135–137 (1876).

    PubMed  PubMed Central  Google Scholar 

  3. Butlin, H.T. Br. med. J. ii, 66–71 (1892).

    Google Scholar 

  4. Yamagiwa, K. & Ichikawa, K. Verh. jap. path. Ges. 5, 142–148 (1915).

    Google Scholar 

  5. Tsutsui, H. Gann 12, 17–21 (1918).

    Google Scholar 

  6. Bloch, B. & Dreifuss, W. Schweiz. med. Wschr. 51, 1033–1037 (1921).

    Google Scholar 

  7. Kennaway, E.L. J. Path. Bact. 27, 233–238 (1924).

    CAS  Google Scholar 

  8. Bertholet, M. C. r.hebd.Séanc. Acad. Sci. Paris, 63, 479–508 (1866).

    Google Scholar 

  9. Kennaway, E.L. Br. med. J. i, 564–567 (1924).

    Google Scholar 

  10. Schroeter, G. Brennst.-Chem. 1, 39–41 (1920).

    CAS  Google Scholar 

  11. Hieger, I. Biochem. J. 24, 505–511 (1930).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Clar, E. Ber. dt. chem. Ges. 62, 350–359 (1929).

    Google Scholar 

  13. Fieser, L.F. & Dietz, E.M. Ber. dt. chem. Ges. 62, 1827–1833 (1929).

    Google Scholar 

  14. Kennaway, E.L. & Hieger, I. Br.med.J. ii, 1044–1046 (1930).

    Google Scholar 

  15. Kennaway, E. Br. med. J. ii, 749–752 (1955).

    Google Scholar 

  16. Cook, J.W., Hewett, C.L. & Hieger, I. J. chem. Soc. 395–405 (1933).

  17. Cook, J.W. Biogr. Mem. Fellows R. Soc. 4, 139–154 (1958).

    Google Scholar 

  18. Cook, J.W., Hieger, I., Kennaway, E.L. & Mayneord, W.V. Proc. R. Soc. B111, 455–484 (1932).

    CAS  ADS  Google Scholar 

  19. Cook, J.W. Proc. R. Soc. B111, 485–495 (1932).

    CAS  ADS  Google Scholar 

  20. Barry, G. et al. Proc. R. Soc. B117, 318–351 (1935).

    CAS  ADS  Google Scholar 

  21. Bachmann, W.E. et al. Proc. R. Soc. B123, 343–368 (1937).

    CAS  ADS  Google Scholar 

  22. Badger, G.M. et al. Proc. R. Soc. B129, 439–467 (1940).

    CAS  ADS  Google Scholar 

  23. Badger, G.M. et al. Proc. R. Soc. B131, 170–182 (1942).

    CAS  ADS  Google Scholar 

  24. Bachmann, W.E. & Chemerda, J.M. J. Am. chem. Soc. 60, 1023–1026 (1938).

    CAS  Google Scholar 

  25. Bachmann, W.E., Kennaway, E.L. & Kennaway, N.M. Yale J. Biol. Med. 11, 97–102 (1938).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Huggins, C.B. Experimental Leukemia and Mammary Cancer: Induction, Prevention, Cure (University of Chicago Press, 1979).

    Google Scholar 

  27. Wieland, H. & Dane, E. Hoppe-Seyler's Z. physiol. Chem. 219, 240–244 (1933).

    CAS  Google Scholar 

  28. Cottini, G.B. & Mazzone, G.B. Am. J. Cancer 37, 186–195 (1939).

    CAS  Google Scholar 

  29. Haddow, A. Nature 136, 868–869 (1935).

    CAS  ADS  Google Scholar 

  30. Pullman, A. Bull. Cancer 33, 120–130 (1946).

    CAS  Google Scholar 

  31. Clar, E. Polycyclic Hydrocarbons Vols 1,2 (Academic, London, 1964).

    Google Scholar 

  32. Schmidt, O. Naturwissenschaften 29, 146–150 (1941).

    CAS  ADS  Google Scholar 

  33. Svartholm, N.V. Ark. Kemi Miner. Geol. A15, no. 13 (1941).

  34. Coulson, C.A. Adv. Cancer Res. 1, 1–56 (1953).

    CAS  PubMed  Google Scholar 

  35. Pullman, A. & Pullman, B. Adv. Cancer Res. 3, 117–169 (1955).

    CAS  PubMed  Google Scholar 

  36. Baumann, E. & Herter, E. Hoppe-Seyler's Z. physiol. Chem. 1, 244–269 (1877).

    Google Scholar 

  37. Bergell, P. & Pschorr, R. Hoppe-Seyler's Z. physiol. Chem. 38, 16–38 (1903).

    CAS  Google Scholar 

  38. Bourne, M.C. & Young, L. Biochem. J. 28, 803–808 (1934).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Boyland, E. & Levi, A.A. Biochem. J. 29, 2679–2683 (1935).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Boyland, E. Biochem. Soc. Symp. 5, 40–54 (1950).

    CAS  Google Scholar 

  41. Boyland, E. & Green, B. Br. J. Cancer 16, 347–360 (1962).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Arcos, J.C. & Argus, M.F. Adv. Cancer Res. 11, 305–471 (1968).

    CAS  PubMed  Google Scholar 

  43. Searle, C.E. (ed.) Chemical Carcinogens ACS Monograph Ser. no. 173 (American Chemical Society, 1976).

  44. Miller, J.A. & Miller, E.C. in Jerusalem Symposia on Quantum Chemistry and Biochemistry Vol.1 (eds Bergmann, E.D. & Pullman, B.) 237–262 (Israel Academy of Sciences and Humanities, Jerusalem, 1969).

    Google Scholar 

  45. Miller, J.A. Cancer Res. 30, 559–576 (1970).

    CAS  PubMed  Google Scholar 

  46. Miller, E.C. Cancer Res. 11, 100–108 (1951).

    CAS  PubMed  Google Scholar 

  47. Miller, E.C. & Miller, J.A. Cancer Res. 7, 468–480 (1947).

    CAS  Google Scholar 

  48. Heidelberger, C. & Davenport, G.R. Acta Un. int. Cancr. 17, 55–63 (1961).

    CAS  PubMed  Google Scholar 

  49. Brookes, P. & Lawley, P.D. Nature 202, 781–784 (1964).

    CAS  PubMed  ADS  Google Scholar 

  50. Holtzman, J.L., Gillette, J.R. & Milne, G.W.A. J. biol. Chem. 242, 4386–4387 (1967).

    CAS  PubMed  Google Scholar 

  51. Conney, A.H., Miller, E.C. & Miller, J.A. J. biol. Chem. 228, 753–766 (1957).

    CAS  PubMed  Google Scholar 

  52. Grover, P.L. & Sims, P. Biochem. J. 110, 159–160 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Gelboin, H.V. Cancer Res. 29, 1272–1276 (1969).

    CAS  PubMed  Google Scholar 

  54. Ames, B.N., Durston, W.E., Yamasaki, E. & Lee, F.D. Proc. natn. Acad. Sci. U.S.A. 70, 2281–2285 (1973).

    CAS  ADS  Google Scholar 

  55. Sims, P. & Grover, P.L. Adv. Cancer Res. 20, 165–274 (1974).

    CAS  PubMed  Google Scholar 

  56. Jerina, D.M., Daly, J.W., Witkop, B., Zaltman-Nirenberg, P. & Udenfriend, S. J. Am. chem. Soc. 90, 6525–6527 (1968).

    CAS  PubMed  Google Scholar 

  57. Grover, P.L., Hewer, A. & Sims, P. FEBS Lett. 18, 76–80 (1971).

    CAS  PubMed  Google Scholar 

  58. Grover, P.L., Hewer, A. & Sims, P. Biochem. Pharmac. 21, 2713–2726 (1972).

    CAS  Google Scholar 

  59. Selkirk, J.K., Huberman, E. & Heidelberger, C. Biochem. biophys. Res. Commun. 43, 1010–1016 (1971).

    CAS  PubMed  Google Scholar 

  60. Wang, I.Y., Rasmussen, R.E. & Crocker, T.T. Biochem. biophys. Res. Commun. 49, 1142–1149 (1972).

    CAS  PubMed  Google Scholar 

  61. Newman, M.S. & Blum, S. J. Am. chem. Soc. 86, 5598–5600 (1964).

    CAS  Google Scholar 

  62. Grover, P.L. & Sims, P. Biochem. Pharmac. 19, 2251–2259 (1970).

    CAS  Google Scholar 

  63. Grover, P.L. et al. Proc. natn. Acad. Sci. U.S.A. 68, 1098–1101 (1971).

    CAS  ADS  Google Scholar 

  64. Huberman, E., Aspiras, L., Heidelberger, C., Grover, P.L. & Sims, P. Proc. natn. Acad. Sci. U.S.A. 68, 3195–3199 (1971).

    CAS  ADS  Google Scholar 

  65. Ames, B.N., Sims, P. & Grover, P.L. Science 176, 47–49 (1972).

    CAS  PubMed  ADS  Google Scholar 

  66. Miller, E.C. & Miller, J.A. Proc. Soc. exp. Biol. Med. 124, 915–919 (1967).

    CAS  PubMed  Google Scholar 

  67. Sims, P. Int. J. Cancer 2, 505–508 (1967).

    CAS  PubMed  Google Scholar 

  68. Van Durren, B.L., Langseth, L., Goldsehmidt, B.M. & Orris, L. J. natn. Cancer Inst. 39, 1217–1228 (1967).

    Google Scholar 

  69. Baird, W.M., Dipple, A., Grover, P.L., Sims, P. & Brookes, P. Cancer Res. 33, 2386–2392 (1973).

    CAS  PubMed  Google Scholar 

  70. Baird, W.M., Harvey, R.G. & Brookes, P. Cancer Res. 35, 54–57 (1975).

    CAS  PubMed  Google Scholar 

  71. Borgen, A. et al. J. med. Chem. 16, 502–506 (1973).

    CAS  PubMed  Google Scholar 

  72. Booth, J., Keysell, G.R. & Sims, P. Biochem. Pharmac. 22, 1781–1791 (1973).

    CAS  Google Scholar 

  73. Booth, J. & Sims, P. FEBS Lett. 47, 30–33 (1974).

    CAS  PubMed  Google Scholar 

  74. Sims, P. Proc. 11th int. Cancer Congr., Florence, 1974 Vol.2, 9–13 (1975).

    Google Scholar 

  75. Sims, P., Grover, P.L., Swaisland, A., Pal, K. & Hewer, A. Nature 252, 326–328 (1974).

    CAS  PubMed  ADS  Google Scholar 

  76. Daudel, P., Duquesne, M., Vigny, P., Grover, P.L. & Sims, P. FEBS Lett. 57, 250–253 (1975).

    CAS  PubMed  Google Scholar 

  77. Ivanovic, V., Geacintov, N.E. & Weinstein, I.B. Biochem. biophys. Res. Commun. 70, 1172–1179 (1976).

    CAS  PubMed  Google Scholar 

  78. Grover, P.L., Hewer, A., Pal, K. & Sims, P. Int. J. Cancer 18, 1–6 (1976).

    CAS  PubMed  Google Scholar 

  79. Chouroulinkov, I., Gentil, A., Grover, P.L. & Sims, P. Br. J. Cancer 34, 523–532 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Slaga, T.J. et al. Cancer Lett. 2, 115–122 (1976).

    CAS  PubMed  Google Scholar 

  81. Levin, W., Wood, A.W., Yagi, H., Jerina, D.M. & Conney, A.H. Proc. natn. Acad. Sci. U.S.A. 73, 3867–3871 (1976).

    CAS  ADS  Google Scholar 

  82. Marquardt, H., Grover, P.L. & Sims, P. Cancer Res. 36, 2059–2064 (1976).

    CAS  PubMed  Google Scholar 

  83. Mager, R., Huberman, E., Yang, S.K., Gelboin, H.V. & Sachs, L. Int. J. Cancer 19, 814–817 (1977).

    CAS  PubMed  Google Scholar 

  84. Malaveille, C., Bartsch, H., Grover, P.L. & Sims, P. Biochem. biophys. Res. Commun. 66, 693–700 (1975).

    CAS  PubMed  Google Scholar 

  85. Thakker, D.R. et al. Chemico-Biol. Interactions 16, 281–300 (1977).

    CAS  Google Scholar 

  86. Yang, S.K., McCourt, D.W., Leutz, J.C. & Gelboin, H.V. Science 196, 1199–1201 (1977).

    CAS  PubMed  ADS  Google Scholar 

  87. Levin, W. et al. J. biol. Chem. 255, 9067–9074 (1980).

    CAS  PubMed  Google Scholar 

  88. Levin, W. et al. Cancer Res. 37, 2721–2725 (1977).

    CAS  PubMed  Google Scholar 

  89. Huberman, E., Yang, S.K., McCourt, D.W. & Gelboin, H.V. Cancer Lett. 4, 35–43 (1977).

    Google Scholar 

  90. Hulbert, P.B. Nature 256, 146–148 (1975).

    CAS  PubMed  ADS  Google Scholar 

  91. Yagi, H., Hernandez, O. & Jerina, D.M. J. Am. chem. Soc. 97, 6881–6883 (1975).

    CAS  PubMed  Google Scholar 

  92. Wood, A.W. et al. Cancer Res. 36, 3358–3366 (1976).

    CAS  PubMed  Google Scholar 

  93. Malaveille, C., Kuroki, T., Sims, P., Grover, P.L. & Bartsch, H. Mutat. Res. 44, 313–326 (1977).

    CAS  PubMed  Google Scholar 

  94. Huberman, E., Sachs, L., Yang, S.K. & Gelboin, H.V. Proc. natn. Acad. Sci. U.S.A. 73, 607–611 (1976).

    CAS  ADS  Google Scholar 

  95. Newbold, R.F. & Brookes, P. Nature 261, 52–54 (1976).

    CAS  PubMed  ADS  Google Scholar 

  96. Marquardt, H., Baker, S., Grover, P.L. & Sims, P. Cancer Lett. 3, 31–36 (1977).

    CAS  PubMed  Google Scholar 

  97. Keller, J.W., Heidelberger, C., Beland, F.A. & Harvey, R.G. J. Am. chem. Soc. 98, 8276–8277 (1976).

    CAS  Google Scholar 

  98. Wood, A.W. et al. Biochem. biophys. Res. Commun. 77, 1389–1396 (1977).

    CAS  PubMed  Google Scholar 

  99. Buening, M.K. et al. Proc. natn. Acad. Sci. U.S.A. 75, 5358–5361 (1978).

    CAS  ADS  Google Scholar 

  100. Levin, W. et al. Cancer Res. 37, 3356–3361 (1977).

    CAS  PubMed  Google Scholar 

  101. Slaga, T.J. et al. Cancer Res. 37, 4130–4133 (1977).

    CAS  PubMed  Google Scholar 

  102. Jennette, K.W. et al. Biochemistry 16, 932–938 (1977).

    CAS  PubMed  Google Scholar 

  103. Meehan, T., Straub, K. & Clavin, M. Nature 269, 725–727 (1977).

    CAS  PubMed  ADS  Google Scholar 

  104. Weinstein, I.B. et al. Science 193, 592–595 (1976).

    CAS  PubMed  ADS  Google Scholar 

  105. Jeffrey, A.M. et al. J. Am. chem. Soc. 98, 5714–5715 (1976).

    CAS  PubMed  Google Scholar 

  106. Koreeda, M., Moore, P.D., Yagi, H., Yeh, H.J.C. & Jerina, D.M. J. Am. chem. Soc. 98, 6720–6722 (1976).

    CAS  PubMed  Google Scholar 

  107. Osborne, M.R., Beland, F.A., Harvey, R.G. & Brookes, P. Int. J. Cancer 18, 362–368 (1976).

    CAS  PubMed  Google Scholar 

  108. Nakanishi, K. et al. J. Am. chem. Soc. 99, 258–260 (1977).

    CAS  PubMed  Google Scholar 

  109. King, H.W.S., Osborne, M.R., Beland, F.A., Harvey, R.G. & Brookes, P. Proc. natn. Acad. Sci. U.S.A. 73, 2679–2681 (1976).

    CAS  ADS  Google Scholar 

  110. Jeffrey, A.M. et al. Nature 269, 348–350 (1977).

    CAS  PubMed  ADS  Google Scholar 

  111. Baird, W.M. & Diamond, L. Biochem. biophys. Res. Commun. 77, 162–167 (1977).

    CAS  PubMed  Google Scholar 

  112. Koreeda, M. et al. Science 199, 778–781 (1978).

    CAS  PubMed  ADS  Google Scholar 

  113. Osborne, M.R., Harvey, R.G. & Brookes, P. Chemico-Biol. Interactions 20, 123–130 (1978).

    CAS  Google Scholar 

  114. Jeffrey, A.M. et al. Science 206, 1309–1311 (1979).

    CAS  PubMed  ADS  Google Scholar 

  115. Meehan, T. & Straub, K. Nature 277, 410–412 (1979).

    CAS  PubMed  ADS  Google Scholar 

  116. Osborne, M.R., Jacobs, S., Harvey, R.G. & Brookes, P. Carcinogenesis 2, 553–558 (1981).

    CAS  PubMed  Google Scholar 

  117. Geacintov, N.E., Gagliano, A., Ivanovic, V. & Weinstein, I.B. Biochemistry 17, 5256–5262 (1978).

    CAS  PubMed  Google Scholar 

  118. Beland, F.A. Chemico-Biol. Interactions 22, 329–339 (1978).

    CAS  Google Scholar 

  119. Kadlubar, F.F. Chemico-Biol. Interactions 31, 255–263 (1980).

    CAS  Google Scholar 

  120. Drinkwater, N.R., Miller, J.A., Miller, E.C. & Yang, N.-C. Cancer Res. 38, 3247–3255 (1978).

    CAS  PubMed  Google Scholar 

  121. Jerina, D.M. et al. in In Vitro Metabolic Activation in Mutagenesis Testing (eds de Serres, F.J., Fouts, J.R., Bend, J.R. & Philpot, R.M.) 159–177 (Elsevier, Amsterdam, 1976).

    Google Scholar 

  122. Jerina, D.M. & Daly, J.W. in Drug Metabolism: from Microbe to Man (eds Parke, D.V. & Smith, R.L.) 13–32 (Taylor and Francis, London, 1977).

    Google Scholar 

  123. Sims, P. & Grover, P.L. in Polycyclic Hydrocarbons and Cancer Vol. 3 (eds Gelboin, H.V. & Ts'o, P.O.P.) 117–181 (Academic, New York, 1981).

    Google Scholar 

  124. Conney, A.H. Cancer Res. 42, 4875–4917 (1982).

    CAS  PubMed  Google Scholar 

  125. Wood, A.W. et al. J. biol. Chem. 251, 4882–4890 (1976).

    CAS  PubMed  Google Scholar 

  126. Cooper, C.S., Hewer, A., Ribeiro, O., Grover, P.L. & Sims, P. Carcinogenesis 1, 1075–1080 (1980).

    CAS  PubMed  Google Scholar 

  127. Yang, S.K., McCourt, D.W. & Gelboin, H.V. J. Am. chem. Soc. 5130–5134 (1977).

    CAS  PubMed  Google Scholar 

  128. Gelboin, H.V. & Ts'o, P.O.P. (eds) Polycyclic Hydrocarbons and Cancer Vols 1,2 (Academic, 1978).

  129. Gelboin, H.V. Physiol. Rev. 60, 1107–1166 (1980).

    CAS  PubMed  Google Scholar 

  130. Cooper, C.S., Grover, P.L. & Sims, P. Prog. Drug Metab. 7, 295–396 (1983).

    CAS  Google Scholar 

  131. Wattenberg, L.W., Leong, J.L. & Strand, P.J. Cancer Res. 22, 1120–1125 (1962).

    CAS  PubMed  Google Scholar 

  132. Selkirk, J.K., Croy, R.G., Roller, P.P. & Gelboin, H.V. Cancer Res. 34, 3474–3480 (1974).

    CAS  PubMed  Google Scholar 

  133. Holder, G.M., Yagi, H., Jerina, D.M., Lu, A.Y.H. & Conney, A.H. Proc. natn. Acad. Sci. U.S.A. 71, 4356–4360 (1974).

    CAS  ADS  Google Scholar 

  134. National Academy of Sciences, Committee on Biologic Effects of Atmospheric Pollutants. Particulate Polycyclic Organic Matter, Washington, DC (1972).

  135. Harris, C.C., Trump, B.F., Grafstrom, R. & Autrup, H. J. cell. Biochem. 18, 285–294 (1982).

    CAS  PubMed  Google Scholar 

  136. Phillips, D.H., Grover, P.L. & Sims, P. Int. J. Cancer 22, 487–494 (1978).

    CAS  PubMed  Google Scholar 

  137. Poirier, M.C., Santella, R., Weinstein, I.B., Grunberger, D. & Yuspa, S.H. Cancer Res. 40, 412–416 (1980).

    CAS  PubMed  Google Scholar 

  138. Perera, F.P. et al. Carcinogenesis 3, 1405–1410 (1982).

    CAS  PubMed  Google Scholar 

  139. Dipple, A. in Chemical Carcinogens (ed. Searle, C.E.) 245–314 (ACS Monograph Ser. no. 173, American Chemical Society, 1976).

    Google Scholar 

  140. Seribner, J.D. J. natn. Cancer Inst. 50, 1717–1719 (1973).

    Google Scholar 

  141. Bauer, K.H. Arch. klin. Chir. 189, 123–184 (1937).

    Google Scholar 

  142. Bauer, K.H., Rarei, B. & Gummel . Arch. klin. Chir. 193, 499–502 (1938).

    Google Scholar 

  143. Huggins, C. & McCarthy, J.D. Cancer Res. 17, 1028–1032 (1957).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Phillips, D. Fifty years of benzo(a)pyrene. Nature 303, 468–472 (1983). https://doi.org/10.1038/303468a0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/303468a0

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing