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Dihydrodiols and Diol-Epoxides in the Activation and Detoxification of Polycyclic Hydrocarbons

  • Peter Sims
Conference paper
Part of the The Jerusalem Symposia on Quantum Chemistry and Biochemistry book series (JSQC, volume 13)

Abstract

The weak carcinogen, benz(a)anthracene, is metabolized to a number of dihydrodiols and diol-epoxides. Hydrolysates of the DNA of mouse skin or of hamster embryo cells treated with the hydrocarbon contain adducts arising from the reactions with the nucleic acid of both the ‘bay- region’ anti-3,4-diol-1,2-epoxide and the non-‘bay-region’ anti-8,9- diol-10,11-epoxide. However, only the 8,9-diol-10,11-epoxide appears to be involved in the reaction of the hydrocarbon with the RNA of hamster embryo cells. In contrast, the activation of the moderately active carcinogen, 7-methylbenz(a)anthracene and the potent carcinogen, 7,12- dimethylbenz(a)anthracene on mouse skin appears to involve mainly the ‘bay-region’ 3,4-diol-1,2-epoxides.

Keywords

Metabolic Activation Sephadex LH20 Mouse Skin Potent Carcinogen Active Carcinogen 
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.

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References

  1. Baird, W.M. and Brookes, P.: 1973, Cancer Res. 33, pp 2378–2385.Google Scholar
  2. Baird, W.M., Dipple, A., Grover, P.L., Sims, P. and Brookes, P.: 1973, Cancer Res. 33, pp 2386–2392.Google Scholar
  3. Booth, J. and Sims, P.: 1974, FEBS Lett.. 47, pp 30–33.CrossRefGoogle Scholar
  4. Boyland, E.: 1950, Biochem.Soc.Symp. 5, pp 40–54.Google Scholar
  5. Chouroulinkov, I., Gentil, A., Tierney, B., Grover, P.L. and Sims, P.: 1977, Cancer Lett. 3, pp 247–253.CrossRefGoogle Scholar
  6. Cooper, C.S., Ribeiro, O., Hewer, A., Walsh, C., Pal., K., Grover, P.L. and Sims, P.: 1980a, Carcinogenesis, in press.Google Scholar
  7. Cooper, C.S., Ribeiro, O., Farmer, P.B., Hewer, A., Walsh, C., Pal, K., Grover, P.L. and Sins, P.: 1980b, Chem.-Biol.Interactions, submittedGoogle Scholar
  8. Cooper, C.S., Ribeiro, 0., Hewer, A., Walsh, C., Grover, P.L. and Sims, P.: 1980c, Chem.-Biol.Interactions, 29, pp 357 - 367.CrossRefGoogle Scholar
  9. Hsu, W.T., Lin, E.J., Fu, P.T., Harvey, R.G. and Weiss, S.B.: 1979, Biochem.Biophys.Res.Commun. 88, pp 251–257.CrossRefGoogle Scholar
  10. Jerina, D.M. and Daly, J.W.: 1977, In Parke, D.V. and Smith, R.L. (eds.) Drug Metabolism - from Microbe to Man, Taylor & Francis. London, PP 13–32.Google Scholar
  11. Jerina, D.M. and Lehr, R.E.: 1977, In Ullrich, V., Roots, I., Hildebrandt, A.G., Esterbrook, R.W. and Conney, A.H. (eds.) Microsomes and Drug Oxidation, Pergamon, Oxford, U.K. pp 709–720.Google Scholar
  12. Keysell, G.R., Booth, J., and Sims, P.: 1975, Xenobiotica, 5, pp 439–448.CrossRefGoogle Scholar
  13. King, H.W.S., Osborne, M.R., Beland, F.A., Harvey, R.G. and Brookes, P.: 1976, Proc.Nacl.Acad.Sci.USA, 73, pp 2679–2681.CrossRefGoogle Scholar
  14. Lehr, R.E., Schaefer-Ridder, M., and Jerina, D.M.: 1976, J.Org.Chem. 42, pp 736–743.CrossRefGoogle Scholar
  15. MacNicoll, A.D., Grover, P.L. and Sims, P.: 1980, Chem.-Biol.Interactions, 29, pp 169–188.CrossRefGoogle Scholar
  16. Malaveille, C., Bartsch, H., Grover, P.L. and Sims, P.: Biochem.Biophys. Res.Commun. 66, pp 693–700.Google Scholar
  17. Malaveille, C., Tierney, B., Grover, P.L., Sims, P. and Bartsch, H.: 1977, Biochem.Biophys.Res.Commun. 75, pp 427–433.CrossRefGoogle Scholar
  18. Malaveille, C., Bartsch, H., Tierney, B., Grover, P.L. and Sims, P.: 1978 Biochem.Biophys.Res.Commun. 83, pp 1468–1473.CrossRefGoogle Scholar
  19. Oesch, F.: 1972, Xenobiotica, 3, pp 305–340.CrossRefGoogle Scholar
  20. Phillips, D.H., Grover, P.L. and Sims, P.: 1979, Int.J.Cancer 23, pp 201–208.CrossRefGoogle Scholar
  21. Sims, P. and Grover, P.L.: 1974, Adv.Cancer Res. 20, pp 165–274.CrossRefGoogle Scholar
  22. Sims, P. and Grover, P.L.: 1976, Med.Biol.Environ. 4, pp 315–329.Google Scholar
  23. Slaga, T.J., Huberman, E., Selkirk, J.K., Harvey, R.G., and Bracken, W.M. 1978, Cancer Res. 38, pp 1699–1704.Google Scholar
  24. Slaga, T.J., Gleason, C.L., DiGiovanni, J., Sukumaran, K.B. and Harvey, R.G.: 1979, Cancer Res. 39, pp 1934–1936.Google Scholar
  25. Swaisland, A.J., Hewer, A., Pal, K., Keysell, G.R., Booth, J., Grover, P. and Sims, P.: 1974, FEBS Lett. 47, pp 34–38.CrossRefGoogle Scholar
  26. Tierney, B., Hewer, A., Walsh, C., Grover, P.L. and Sims, P.: 1977, Chem. Biol.Interactions 18, pp 179–193.CrossRefGoogle Scholar
  27. Tiemey, B., Hewer, A., MacNicoll, A.D., Gervasi, P.G., Rattle, H., Walsh, C., Grover, P.L. and Sims, P.: 1978, Chem.-Biol.Interactions 23, pp 243–257.CrossRefGoogle Scholar
  28. Vigny, P., Kindts, M., Duquesne, M., Cooper, C.S., Grover, P.L. and Sims, P: 1980, Carcinogenesis I, pp 33–36.CrossRefGoogle Scholar
  29. Wislocki, P.G., Kapitulnik, J., Levin, W., Lehr, R., Schaefer-Ridder, M., Karle, J.M., Jerina, D.M. and Conney, A.H.: 1978, Cancer Res. 38, pp 693–696.Google Scholar
  30. Wood, A.W., Levin, W., Lu, A.Y.H., Ryan, D., West, S.B., Lehr, R.E., Schaefer-Ridder, M., Jerina, D.M. and Conney, A.H.: 1976, Biochem.Biophys Res.Commun. 72, pp 680–686.CrossRefGoogle Scholar
  31. Wood, A.W., Levin, W., Chang, R.L., Lehr, R.E., Schaefer-Ridder, M., Karle, J.M., Jerina, D.M. and Conney, A.H.: 1977, Proc.Natl.Acad.Sei.USA, 74, pp 3176–3179.CrossRefGoogle Scholar
  32. Wood, A.W., Levin, W., Thakker, D.R., Yagi, H., Chang, R.L., Ryan, D.E., Thomas, P.E., Dansette, P.M., Whittaker, N., Turujman, S., Lehr, R.E., Kumar, S., Jerina, D.M. and Conney, A.H.: 1979, J.Biol.Chem. 254, pp 4408–4415.Google Scholar

Copyright information

© D. Reidel Publishing Company 1980

Authors and Affiliations

  • Peter Sims
    • 1
  1. 1.Chester Beatty Research InstituteInstitute of Cancer Research:Royal Cancer HospitalLondonEngland

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