Covalent Reactions in the Toxicity of SO2 and Sulfite

  • Daniel B. Menzel
  • DOuglas A. Keller
  • Kwan-Hang Leung
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


Sulfur dioxide (SO2) is a major urban air pollutant, resulting from combustion of sulfur containing fossil fuels. It readily dissolves in water forming sulfurous acid, which dissociates to form bisulfite and sulfite ions (collectively referred to as sulfite), in a ratio depending on the pH of the solution (Petering and Shih, 1975):
$$S{{O}_{2}}+{{H}_{2}}O\rightleftharpoons {{H}^{+}}+HS{{O}_{3}}^{-}\rightleftharpoons 2{{H}^{+}}+S{{O}_{3}}{{^{2}}^{-}}$$
Sulfur dioxide and sulfite are also commonly used as antimicrobial and antioxidant agents in the preservation of foods and beverages (Chichester and Tanner, 1972).


Polycyclic Aromatic Hydrocarbon A549 Cell Fetal Calf Serum Sulfur Dioxide Glutathione Disulfide 
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. Amdur, M. O., 1969. Toxicological appraisal of particulate matter, oxides of sulfur and sulfuric acid. J. Air Pollution Control Assoc. 19, 638–646.CrossRefGoogle Scholar
  2. Babson, J. R. and D. J. Reed, 1978. Inactivation of glutathione reductase by 2-chloroethyl nitrosoureaderived isocyanates. Biochem. Biophys. Res. Comm. 83, 754–762.CrossRefGoogle Scholar
  3. Ball, L. M., J. L. Plummer, B. R. Smith and J. R. Bend, 1979. Benzo(a)pyrene oxidation, conjugation and disposition in the isolated perfused rabbit lung: role of glutathione transferases. Med. Biol. 57, 298–305.PubMedGoogle Scholar
  4. Carlberg, I. and B. Mannervik, 1975. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J. Biol. Chem. 250, 5475–5480.PubMedGoogle Scholar
  5. Chichester, D. F. and F. W. Tanner, Jr., 1972. Antimicrobial food additives. In Handbook of Food Additives ( T. E. Furia ed.), 2nd ed., pp. 115–184. CRC Press, Cleveland.Google Scholar
  6. Eriksson, B. and M. Rundfelt, 1968. Reductive decomposition of S-sulfoglutathione in rat liver. Acta Chem. Scand. 22, 562–570.PubMedCrossRefGoogle Scholar
  7. Gregory, R. E. and A. F. Gunnison, 1984. Identification of plasma proteins containing sulfite-reactive disulfide bonds. Chem.-Biol. Interact. 49, 55–69.PubMedCrossRefGoogle Scholar
  8. Gunnison, A. F., 1981. Sulfite toxicity: A critical review of in vitro and in vivo data. Fd. Cosmet. Toxicol. 19, 667–682.CrossRefGoogle Scholar
  9. Gunnison, A. F. and A. W. Benton, 1971. Sulfur dioxide:sulfite, interactions with mammalian serum and plasma. Arch. Environ. Health 22, 381–388.PubMedGoogle Scholar
  10. Habig, W. H., M. J. Pabst and W. B. Jakoby, 1974. Glutathione S-transferases: The first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249, 7130–7139.PubMedGoogle Scholar
  11. Harris, J. W. and H. M. Patt, 1969. Non-protein sulfhydryl content and cell cycle dynamics of Erlich ascites tumor. Exp. Cell Res. 56, 134–141.PubMedCrossRefGoogle Scholar
  12. Harris, J. W. and S. S. Teng, 1972. Sulfhydryl groups during the S phase: Comparison of cells from G1, plateau phase G1, and G0. J. Cell Physiol. 81, 91–96.CrossRefGoogle Scholar
  13. Hesse, S., B. Jernstrom, M. Martinez, P. Moldeus, L. Christoulides and B. Ketterer, 1982. Inactivation of DNA binding metabolites of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol by glutathione and glutathione S-transferases. Carcinogenesis 3, 757–760.PubMedCrossRefGoogle Scholar
  14. Jernstrom, B., L. Dock and M. Martinez, 1984. Metabolic activation of benzo(a)pyrene-7,8-dihydrodiol and benzo(a)pyrene-7,8-dihydrodiol-9,10,epoxide to protein binding products and the inhibition effect of glutathione and cysteine. Carcinogenesis 5, 199–204.PubMedCrossRefGoogle Scholar
  15. Keller, D. A. and D. B. Menzel, 1985. Picomole analysis of glutathione, glutathione disulfide, glutathione Ssulfonate, and cysteine S-sulfonate by HPLC. Analytical Biochemistry (submitted).Google Scholar
  16. Koenig, J. Q., W. E. Paison, M. Horike and R. Frank, 1983. A comparison of the pulmonary effects of 0.5 ppm versus 1.0 ppm sulfur dioxide plus sodium chloride droplets in asthmatic adolescents. J. Tox. Environ. Health 11, 129–139.CrossRefGoogle Scholar
  17. Laskin, S., M. Kuschner, A. Sellakuman and G. V. Katz, 1976. Combined carcinogen-irritant animal inhalation studies. In Air Pollution and the Lung ( E. F. Aharoson, A. Ben-David and M. A. Klingberg, eds.), pp. 190–213. Wiley, New York.Google Scholar
  18. Leung, K.-H., G. B. Post and D. B. Menzel, 1985.Google Scholar
  19. Glutathione S-sulfonate, a sulfur dioxide metabolite, as a competitive inhibitor of glutathione Stransferase, and its reduction by glutathione reductase. Toxicol. Appl. Pharm. 77, 388–394.Google Scholar
  20. Leung, K.-H. and D. B. Menzel, 1985a. Formation of glutathione conjugate of benzo(a)pyrene epoxides in vitro and its inhibition by glutathione S-sulfonate. Toxicol. Appl. Pharm. (submitted).Google Scholar
  21. Linn, W. S., T. G. Venet, D. A. Shamoo, L. M. Valencia, U. T. Anzai, C. E. Spier, and J. D. Hackney, 1983. Respiratory effects of sulfur dioxide in heavily exercising asthmatics. Am. Rev. Respir. Dis. 127, 287–283.Google Scholar
  22. Ohara, H. and T. Terasima, 1969. Variations of cellular sulfhydryl content during cell cycle of HeLa cells and its correlation to cyclic change of X-ray sensitivity. Exp. Cell Res. 58, 182–185.PubMedCrossRefGoogle Scholar
  23. Petering, D. F. and N. T. Shih, 1975. Biochemistry of bisulfite–sulfur dioxide. Environmental Res. 9, 55–65.CrossRefGoogle Scholar
  24. Pott, F. and W. Stober, 1983. Carcinogenicity of airborne combustion products observed in subcutaneous tissue and lungs of laboratory rodents. Environ. Health Perspect. 47, 293–303.PubMedCrossRefGoogle Scholar
  25. Post, G. B., D. A. Keller, K. A. Conner and D. B. Menzel, 1983. Effects of culture conditions on glutathione content in A549 cells. Biochem. Biophys. Res. Comm. 114, 737–742.PubMedCrossRefGoogle Scholar
  26. Reed, D. J., J. R. Babson, P. W. Beatty, A. E. Brodie, W. W. Ellis and D. W. Potter, 1980. High-performance liquid chromatograph analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides. Anal. Biochem. 106, 55–62.PubMedCrossRefGoogle Scholar
  27. Shapiro, R., 1977. Genetic effects of bisulfite (sulfur dioxide). Mutation Res. 39, 149–176.PubMedGoogle Scholar
  28. Smith, B. R., J. L. Plummer, L. M. Ball and J. R. Bend, 1980. Characterization of pulmonary arene oxide biotransformation using the perfused rabbit lung. Cancer Res. 40, 101–106.PubMedGoogle Scholar
  29. Waley, S. G., 1959. Acidic peptides of the lens. 5. Ssulfoglutathione. Biochem. J. 71, 132–137.Google Scholar
  30. Winnell, M. and B. Mannervik, 1969. The nature of the enzymatic reduction of Ssulfoglutathione in liver and peas. Biochem. Biophys. Acta 184, 374–380.CrossRefGoogle Scholar
  31. West, P. W. and G. C. Gaeke, 1956. fixation of sulfur dioxide as disulfitomercurate (II) and subsequent colorimetric estimation. Anal. Chem. 28, 1816–1819.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Daniel B. Menzel
    • 1
  • DOuglas A. Keller
    • 1
  • Kwan-Hang Leung
    • 1
  1. 1.Depts. of Pharmacology and Medicine, Comprehensive Cancer CenterDuke Univ Med CtrDurhamUSA

Personalised recommendations