Human Health Risk Assessment and Biological Reactive Intermediates: Hemoglobin Binding

  • L. Ehrenberg
  • Margareta Tornqvist
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


There is ample evidence to show that the demonstration of adducts to hemoglobin and other proteins of electrophilically reactive compounds or biological reactive intermediates (BRI) is a relevant indication of the formation of the corresponding DNA adducts, and also that the rates of formation of protein- and DNA adducts are proportional. Measurement of hemoglobin and DNA adducts are therefore complementary. The former has so far been used mainly in the monitoring of lowmol.wt alkylators and BRI whereas DNA adduct monitoring has been applicable mostly to bulky compounds.


Ethylene Oxide Ethene Oxide Propylene Oxide Styrene Oxide Adduct Level 
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. Bryant, M.S., Skipper, P.L., Tannenbaum, S.R. and Maclure, M. (1987). Hemoglobin adducts of 4-aminobiphenyl in smokers and non-smokers. Cancer Res. 47, 602–608.Google Scholar
  2. Calleman, C.-J., Ehrenberg, L., Jansson, B., Osterman-Golkar, S., Segerbäck, D., Svensson, K. and Wachtmeister, C.A. (1978). Monitoring and risk assessment by means of alkyl groups in hemoglobin in persons occupationally exposed to ethylene oxide. J. Environ. Pathol. Toxicol. 2, 427–442.PubMedGoogle Scholar
  3. Christakopoulos, A., Svensson, K., Bergmark, E. and Osterman-Golkar S. (1989). Monitoring of styrene exposure through hemoglobin adducts by the modified Edman procedure. To be published.Google Scholar
  4. Duus, U., Osterman-Golkar, S., Törnqvist, M., Mowrer, J., Holm, S. and Ehrenberg, L. 1989 ). Studies of determinants of tissue dose and cancer risk from ethylene oxide exposure. In Proc. Symp. Management of Risk from Genotoxic Substances in the Environment ( L. Freij, Ed.), pp. 141–153. Swedish National Chemicals Inspectorate, Solna, Sweden.Google Scholar
  5. Ehrenberg, L. (1979). Risk assessment of ethylene oxide and other compounds. In A,ssessing Chgmical Mutagens: The Risk to Humans (V.K. McElheny and S. Abrahamson, Eds) Banbury Rep., 1, pp. 157–190. Cold Spring Harbor Laboratory.Google Scholar
  6. Ehrenberg, L. (1980). Purposes and methods of comparing effects of radiation and chemicals. In Radiobiological Equivalents of Chemical Pollutants, pp. 11–22, 23–36. IAEA, Vienna.Google Scholar
  7. Ehrenberg, L. (1984). Aspects of statistical inference in testing for genetic toxicity. In Handbook of Mutagenicity Test Procedures, 2nd Edition ( B.J. Kilbey et al. Eds) pp. 775–822. Elsevier, Amsterdam.Google Scholar
  8. Ehrenberg, L. and Osterman-Golkar, S. (1980). Alkylation of macromolecules for detecting mutagenic agents. Teratog. Carcinog. Mutag. 1, 105–127.CrossRefGoogle Scholar
  9. Ehrenberg, Moustacchi, E. and Osterman-Golkar, S. (1983). Dosimetry of genotoxic agents and dose-response relationships of their effects. Mutat. Res. 123, 121–182.Google Scholar
  10. Ehrenberg, L., Osterman-Golkar, S., Segerbäck, D. and Törnqvist, M. (1986). Power of methods for monitoring exposure to genotoxic chemicals by covalently bound adducts to macromolecules. In Environmental Mutagenesis and Carcinogenesis ( N.K. Notani and P.S. Chauhan Eds), pp. 155–166. Bhabha Atomic Research Centre, Bombay.Google Scholar
  11. Everson, R.B., Randerath, E., Santella, R.M. et al. (1986). Detection of smoking- related covalent DNA adducts in human placenta. Science 231, 54–57.CrossRefPubMedGoogle Scholar
  12. Farmer, P.B., Neumann, H.-G. and Henschler, D. (1987). Estimation of exposure of man to substances reacting covalently with macromolecules. Arch. Toxicol. 60, 251–260.Google Scholar
  13. Gupta, R.C. and Randerath, K. (1988). Analysis of DNA adducts by 32P labelling and thin layer chromatography. In DNA Repair ( E.C. Friedberg and P.C. Hanawalt, eds) Marcel Dekker, New York.Google Scholar
  14. Higginson, J. and Muir, C.S. (1979). Environmental carcinogenesis: Misconceptions and limitations to cancer control. J. Natl. Cancer Inst. 63, 1291–1298.PubMedGoogle Scholar
  15. Hgstedt, B., Bergmark, E., Törnqvist, M. and Osterman-Golkar, S. (1990). Chromosomal aberrations and micronuclei in lymphocytes in relation to alkylation of hemoglobin in workers exposed to ethylene oxide and propylene oxide (manuscript).Google Scholar
  16. ICRP Publication No. 26 (1977). Recommendations of the International Commission on Radiological Protection. Ann. ICRP, Vol. 1, No 3, Pergamon Press, Oxford.Google Scholar
  17. Kautiainen, A., Törnqvist, M., Svensson, K. and Osterman-Golkar, S. (1989). Adducts of malonaldehyde and a few other aldehydes to hemoglobin. Carcinogenesis 10, 2123–2130.CrossRefPubMedGoogle Scholar
  18. Kautiainen, A., Osterman-Golkar, S. and Ehrenberg, L. (1986). Misincorporation of alkylated amino acids into hemoglobin–a possible source of background alkylations. Acta Chem. Scand. B, 40, 453–456.CrossRefGoogle Scholar
  19. Osterman-Golkar, S., Bailey, E., Farmer, P.B., Gorf, S.M. and Lamb, J.H. (1984). Monitoring exposure to propylene oxide through the determination of hemoglobin alkylation. Scand. J. Work Environ. Health 10, 99–102.CrossRefPubMedGoogle Scholar
  20. Osterman-Golkar, S., Ehrenberg, L. and Wachtmeister, C.A. (1970). Reaction kinetics and biological action in barley of monofunctional methanesulfonic esters. Radiat. Botany 10, 303–327.Google Scholar
  21. Osterman-Golkar, S., Ehrenberg, L., Segerbäck, D. and Hällström, I. (1976).Google Scholar
  22. Evaluation of genetic risks of alkylating agents. II. Haemoglobin as a dose monitor. Mutat. Res. 34, 1–10.Google Scholar
  23. Paracelsus (1538) See Deichmann, W.B., Henschler, D., Holmstedt, B. and Keil, G. (1986). What is there that is not poison? A study of the Third Defence by Paracelsus. Arch. Toxicol. 58, 207–213.Google Scholar
  24. Phillips, D.H., Hemminki, K., Alhonen, A., Hewer, A. and Grover, P.L. (1988a). Monitoring occupational exposure to carcinogens: detection by 32P-postlabelling of aromatic DNA adducts in white blood cells from iron foundry workers. Mutat. Res. 204, 531–541.Google Scholar
  25. Phillips, D.H., Hewer, A., Martin, C.N., Garner, C.G. and King, M.M. (1988b). Correlation of DNA adduct levels in human lung with cigarette smoking. Nature 336, 790–792.CrossRefPubMedGoogle Scholar
  26. Segerbäck, D. (1983). Alkylation of DNA and hemoglobin in the mouse after exposure to ethene and ethene oxide. Chem.-Biol. Interactions 45, 139–151.CrossRefGoogle Scholar
  27. Segerbäck, D. (1985). In vivo dosimetry of some alkylating agents.s a basis for risk estimation. Ph.D. Thesis, University of Stockholm, Stockholm.Google Scholar
  28. Segerbäck, D. (1990). Reaction product in hemoglobin and DNA after in vitro treatment with ethylene oxide and N-(2-hydroxyethyl)-N-nitrosourea. Carcinogenesis 11. (In press.)Google Scholar
  29. Segerbäck, D. and Ehrenberg, L. (1981). Alkylating properties of dichlorvos (DDVP). Acta Pharmacol. Toxicol. 49, Suppl. 5, 56–66.Google Scholar
  30. Svensson, K. and Osterman-Golkar, S. (1987). In vivo 2-oxoethyl adducts in hemoglobin and their possible origin. In Application of Short-Term Bioassays in the Analysis of Complex Environmental Mixtures V (S.S. Sandhu et al., Eds), pp. 49–66. Plenum Press, New York.Google Scholar
  31. Turtóezky, I. and Ehrenberg, L. (1969). Reaction rates and biological action of alkylating agents preliminary report on bactericidal and mutagenic action in E.coli. Mutat. Res. 8, 229–238.Google Scholar
  32. Törnqvist, M. (1988). Search for unknown adducts: increase of sensitivity through preselection by biochemical parameters. IARC Sci. Publ. 89, 378–383.PubMedGoogle Scholar
  33. Törnqvist, M. (1989). Monitoring and cancer risk assessment of carcinogens, particularly alkenes in urban air. Ph.D. Thesis, University of Stockholm, Stockholm.Google Scholar
  34. Törnqvist, M. (1990). The N-alkyl Edman method for hemoglobin adduct measurement: Updating and applications to humans. (In press.)Google Scholar
  35. Törnqvist, M., Segerbäck, D. and Ehrenberg, L. (1990). The “rad-equivalence approach” for ssessment and evaluation of cancer risks, exemplified by studies ofethylene oxide and ethene. (In press.)Google Scholar
  36. Törnqvist, M., Mowrer, J., Jensen, S. and Ehrenberg, L., (1986a). Monitoring of environmental cancer initiators through hemoglobin adducts by a modified Edman degradation method. Anal. Biochem. 154, 255–266.CrossRefPubMedGoogle Scholar
  37. Törnqvist, M., Osterman-Golkar, S., Kautiainen, A., Jensen, S., Farmer, P.B. and Ehrenberg, L. (1986b). Tissue doses of ethylene oxide in cigarette smokers determined from adduct levels in hemoglobin. Carcinogenesis 7, 1519–1521.CrossRefPubMedGoogle Scholar
  38. Törnqvist, M., Kautiainen, A., Gatz, R.N. and Ehrenberg, L. (1988a). Hemoglobin adducts in animals exposed to gasoline and diesel exhausts. 1. Alkenes. J. Appl. Toxicol. 8, 159–170.CrossRefPubMedGoogle Scholar
  39. Törnqvist, M., Osterman-Golkar, S., Kautiainen, A., Nislund, M., Calleman, C.J. and Ehrenberg, L. (1988b). Methylations in human hemoglobin. Mutat. Res. 204, 521–529.CrossRefPubMedGoogle Scholar
  40. Törnqvist, M., Almberg, J., Nilsson, S. and Osterman-Golkar, S. (1989a). Ethene oxide doses in ethene exposed fruit store workers. Scand. J. Work Environ. Health 15, 436–438.CrossRefPubMedGoogle Scholar
  41. Törnqvist, M., Gustafsson, B., Kautiainen, A., Harms-Ringdahl, M., Granath, F. and Ehrenberg, L. (1989b). Unsaturated lipids and intestinal bacteria as sources of endogenous production of ethene and ethylene oxide. Carcinogenesis 10, 39–41.CrossRefPubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • L. Ehrenberg
    • 1
  • Margareta Tornqvist
    • 1
  1. 1.Department of RadiobiologyUniversity of StockholmStockholmSweden

Personalised recommendations