Erythrocyte-Mediated Metabolic Activation Detected by SCE

  • Hannu Norppa
  • Francesco Tursi


Microsomal metabolism has proved to be essential for the acti vation of many chemical carcinogens. For this reason in vitro mutagenicity tests include a metabolic activation system. As a rule, the metabolizing mixtures are prepared from the postmitochondrial fraction of rodent liver. While it is generally accepted that the liver is the primary organ of xenobiotic metabolism for a number of chemicals, it is also known that other tissues can contribute both to the activating and inactivating reactions. The ratio between activation and inactivation may be an important parameter in determining the target tissue of a precarcinogen. However, S-9 mixes from sources other than the liver have only seldom been used in mutagenicity tests.


Human Lymphocyte Sodium Selenite Sister Chromatid Exchange Mutagenicity Test Styrene Oxide 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Whitlock, J.P., H.L. Cooper, and H.V. Gelboin (1972) Aryl hydrocarbon (benzopyrene) hydroxylase is stimulated in human lymphocytes by mitogens and benz(a)anthracene. Science 177: 618–619.PubMedCrossRefGoogle Scholar
  2. 2.
    Okano, P., H.N. Miller, R.C. Robinson, and H.V. Gelboin (1979) Comparison of benzo(a)pyrene and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene metabolism in human blood monocytes and lymphocytes. Cancer Res. 39:3184–3193.PubMedGoogle Scholar
  3. 3.
    Waalkens, D.H., H.F.P. Joosten, R.D.F.M. Taalman, J.M.J.C. Scheres, T.D. Yih, and A. Hoekstra (1981) Sister-chromatid ex-changes induced in vitro by cyclophosphamide without exogenous metabolic activation in lymphocytes from three mammalian spe-cies. Toxicol. Lett. 7:229–232.PubMedCrossRefGoogle Scholar
  4. 4.
    Rüdiger, H.W., F. Kohl, W. Mangels, P. von Wichert, C.R. Bartram, W. Wöhler, and E. Passarge (1976) Benzypyrene induces sister chromatid exchanges in cultured human lymphocytes. Nature 262:290–292.PubMedCrossRefGoogle Scholar
  5. 5.
    Ray, J.H., and L.C. Altenburg (1978) Sister-chromatid exchange induction by sodium selenite: Dependence on the presence of red blood cells or red blood cell lysate. Mutat. Res. 54:343– 354.PubMedCrossRefGoogle Scholar
  6. 6.
    Ray, J.H., and L.C. Altenburg (1982) Sister-chromatid exchange induction by sodium selenite. Plasma protein-bound selenium is not the active SCE-inducing metabolite of Na2SeO3. Mutat. Res .102:285–296.PubMedCrossRefGoogle Scholar
  7. 7.
    Norppa, H., and H. Vainio (1983) Genetic toxicity of styrene and some of its derivatives. Scand. J. Work Environ. Health 9:108–114.PubMedCrossRefGoogle Scholar
  8. 8.
    Watabe, T., A. Hiratsuka, T. Aizawa, T. Sawahata, N. Ozawa, M. Isobe, and E. Takabatake (1982) Studies on metabolism and toxi-city of styrene IV. 1-Vinyl-benzene 3,4-oxide, a potent mutagen formed as a possible intermediate in the metabolism of styrene to 4-vinylphenol. Mutat. Res. 93:45–55.PubMedCrossRefGoogle Scholar
  9. 9.
    Linnainmaa, K., T. Meretoja, M. Sorsa, and H. Vainio (1978) Cytogenetic effects of styrene and styrene oxide. Mutat. Res .58:277–286.PubMedCrossRefGoogle Scholar
  10. 10.
    Norppa, H., M. Sorsa, P. Pfäffli, and H. Vainio (1980) Styrene and styrene oxide induce SCEs and are metabolised in human lym-phocyte cultures. Carcinogenesis 1:357–361.PubMedCrossRefGoogle Scholar
  11. 11.
    Norppa, H., H. Vainio, and M. Sorsa (1983) Metabolic activation of styrene by erythrocytes detected as increased sister chroma-tid exchanges in cultured human lymphocytes. Cancer Res. 43: 3579–3582.PubMedGoogle Scholar
  12. 12.
    Belvedere, G., and F. Tursi (1981) Styrene oxidation to styrene oxide in human blood erythrocytes and lymphocytes. Res. Comm. Chem. Pathol. Pharmacol. 33:273–282.Google Scholar
  13. 13.
    Vainio, H., F. Tursi, and G. Belvedere (1982) What are the sig-nificant toxic metabolites of styrene? In Cytochrome P-450, Biochemistry, Biophysics and Environmental Implications, E. Hietanen, M. Laitinen, and O. Hänninen, eds. Elsevier Biomedi-cal Press B.V., pp. 679–687.Google Scholar
  14. 14.
    Norppa, H., F. Tursi, and P. Einistö (1984) Erythrocytes as a metabolic activation system in mutagenicity tests. In Proceed-ings of the 13th Annual Meeting of the European Environmental Mutagen Society, September 5–9 1983, Montpellier, France. Inserm Symposia Series, Paris (in press).Google Scholar
  15. 15.
    Bauer, C., C. Leporini, G. Bronzetti, C. Corsi, R. Nieri, R. Del Carratore, and S. Tonarelli (1980) The problem of negative results for styrene in the in vitro mutagenesis test with meta-bolic activation (microsomal assay): Explanation by gas chrom-otographic analysis. Boll. Soc. Ital. Biol. Sper. 56:203–207.PubMedGoogle Scholar
  16. 16.
    de Raat, W.K. (1978) Induction of sister chromatid exchanges by styrene and its presumed metabolite styrene oxide in the pre-sence of rat liver homogenate. Chem.-Biol. Interact. 20:163– 170.PubMedCrossRefGoogle Scholar
  17. 17.
    Tursi, F., M. Samaia, and G. Belvedere (1983) Styrene oxidation to styrene oxide in human erythrocytes is catalyzed by oxyhemo-globin. Experientia 39:593–594.PubMedCrossRefGoogle Scholar
  18. 18.
    Belvedere, G., F. Tursi, and H. Vainio (1983) Non-microsomal activaton of styrene to styrene oxide. In Extrahepatic Drug Metabolism and Chemical Carcinogenesis, J. Rydström, J. Montelius, and M. Bengtsson, eds. Elsevier Science Publishers B.V., pp. 193–200.Google Scholar
  19. 19.
    Cantoni, L., D. Blezza, and G. Belvedere (1982) Effect of iron and hemoproteins on hydrogen peroxide-supported styrene oxida-tion to styrene oxide. Experientia 38:1192–1194.PubMedCrossRefGoogle Scholar
  20. 20.
    Mieyal, J.J., R.S. Ackerman, J.L. Blumer, and L.S. Freeman (1976) Characterization of enzyme-like activity of human hemo-globin. Properties of the hemoglobin-P-450 reductase-coupled aniline hydroxylase system. J. Biol. Chem. 251:3436–3441.PubMedGoogle Scholar
  21. 21.
    Yamabe, H., and W. Lovenberg (1972) Decarboxylation of 3,4-di-hydroxyphenylalanine by oxyhemoglobin. Biochem. Biophys. Res. Comm. 47:733–739.PubMedCrossRefGoogle Scholar
  22. 22.
    Meretoja, T., H. Vainio, M. Sorsa, and H. Härkönen (1977) Occu-pational styrene exposure and chromosomal aberrations. Mutat. Res. 56:193–197.CrossRefGoogle Scholar
  23. 23.
    Andersson, H.C., E.Å. Tranberg, A.H. Uggla, and G. Zetterberg (1980) Chromosomal abberations and sister-chromatid exchanges in lymphocytes of men occupationally exposed to styrene in a plastic boat factory. Mutat. Res. 73:387–401.PubMedCrossRefGoogle Scholar
  24. 24.
    Camurri, L., S. Codeluppi, C. Pedroni, and L. Scarduelli (1983) Chromosomal aberrations and sister-chromatid exchanges in work-ers exposed to styrene. Mutat. Res. 119:361–369.PubMedCrossRefGoogle Scholar
  25. 25.
    Byfält Nordqvist, M., E. Gullstrand, E. Lundgren, E.-M. Nydahl, A. Löf, and E. Wigaeus (1983) Förekomst av styren-7,8-oxid och styrenglykol i mus och människa efter administrering av styren. In 32:a Nordiska Yrkeshygieniska Mötet, September 19–21 1983, Stockholm, Sweden. Arbetarskyddsstyrelsen, Stockholm, pp. 77– 78.Google Scholar
  26. 26.
    Norppa, H. (1981) The in vitro induction of sister chromatid exchanges and chromosome aberrations in human lymphocytes by styrene derivatives. Carcinogenesis 3:237–242.CrossRefGoogle Scholar
  27. 27.
    Norppa, H., and H. Vainio (1983) Induction of sister-chromatid exchanges by styrene analogs in cultured human lymphocytes. Mutat. Res. 116:379–387.PubMedCrossRefGoogle Scholar
  28. 28.
    Tursi, F., and H. Norppa (unpublished data).Google Scholar
  29. 29.
    Norppa, H., and F. Tursi (1983) Induction of sister chromatid exchanges by vinyl compounds in cultured human lymphocytes. In Nordic Symposium on Factors Affecting Mutagenicity and Evaluation of Mutagenicity Data. June 8–10 1983., Stockholm, Sweden, Abstracts, pp. 25.Google Scholar
  30. 30.
    Mäki-Paakkkanen, J., F. Tursi, H. Norppa, H. Järventaus, and M. Sorsa (1983) Vinylacetate is a potent inducer of chromosome damage in cultured mammalian cells. In 13th Annual Meeting of European Environmental Mutagen Society. September 5–9 1983, Montpellier, France, Abstracts, II-3-C-7.Google Scholar
  31. 31.
    Norppa, H., and H. Järventaus (unpublished data).Google Scholar
  32. 32.
    Böhlke, J.U., S. Singh, and H.W. Goedde (1983) Cytogenetic effects of acetaldehyde in lymphocytes of Germans and Japanese: SCE, clastogenic activity, and cell cycle delay. Human Genet .63:285–289.CrossRefGoogle Scholar
  33. 33.
    Hopkin, J.M., and P.E. Perry (1980) Benzo(a)pyrene does not contribute to the SCEs induced by cigarette smoke condensate. Mutat. Res. 77:377–381.PubMedCrossRefGoogle Scholar
  34. 34.
    Wilmer, J.L., G.L. Erexson, and A.D. Kligerman (1984) The effect of erythrocytes and hemoglobin on sister chromatid ex-change (SCE) induction in cultured human lymphocytes exposed to aniline HC1. In Sister Chromatid Exchange, R.R. Tice and A. Hollaender, eds. Plenum Press, New York.Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Hannu Norppa
    • 1
  • Francesco Tursi
    • 2
  1. 1.Institute of Occupational HealthHelsinki 29Finland
  2. 2.Istituto di Ricerche Farmacologiche “Mario Negri,”MilanItaly

Personalised recommendations