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Activation of the Immune System and Systemic Immune-Complex Deposits in Brown Norway Rats with Dental Amalgam Restorations

Department of Health and Environment, Division of Molecular and Immunological Pathology, Linkoping University, Linkoping, Sweden

U. Lindh

Department of Diagnostic Radiology, Division of Biomedical Radiation Sciences, Uppsala University, and Centre for Metal Biology, Uppsala, Sweden

P. Horsted-Bindslev

Department of Dental Pathology, Operative Dentistry,and Endodontics, The Royal Dental College, University of Aarhus, DK-8000 Aarhus, Denmark

Dental amalgam restorations are a significant source of mercury exposure in the human population, but their potential to cause systemic health effects is highly disputed. We examined effects on the immune system by giving genetically mercury-susceptible Brown Norway (BN) rats and mercury-resistant Lewis (LE) rats silver amalgam restorations in 4 molars of the upper jaw, causing a body burden similar to that described in human amalgam-bearers (from 250 to 375 mg amalgam/kg body weight). BN rats with amalgam restorations, compared with control rats given composite resinous restorations, developed a rapid activation of the immune system, with a maximum 12-fold increase of the plasma IgE concentration after 3 wks (p < 0.001; Mann-Whitney's test). LE rats receiving amalgam restorations showed no significant increase of plasma IgE (p > 0.05). After 12 wks, BN rats with amalgam restorations showed significantly increased (p < 0.05) titers of immune-complex (IC) deposits in the renal glomeruli and in the vessel walls of internal organs. These rats also showed a significant (p < 0.05), from six- to 130-fold, increase in tissue mercury concentration in the concentration order kidney > spleen > cerebrum occipital lobe > cerebellum > liver > thymus, and the tissue silver concentration was significantly (p < 0.05) increased from three- to 11-fold. Amalgam-implanted BN rats showed a significant (p < 0.05) increase in copper concentration in the kidney and spleen, and in kidney selenium concentration. We conclude that dental amalgam restorations release substantial amounts of their elements, which accumulate in the organs and which, in genetically susceptible rats, give rise to activation of the immune system and systemic IC deposits.

Key Words: rats • amalgam restorations • mercury • silver • autoimmunity

REFERENCES

• Aposhian HV, Bruce DC, Alter W., Dart RC, Hurlbut KM, Aposhian MM (1992). Urinary mercury after administration of 2,3-dimercaptopropane-l-sulfonic acid: correlation with dental amalgam score. FASEB J 6:2472-2476.[Abstract]
• Aten J., Veninga A., De Heer E., Rozing J., Nieuwenhuis P., Hoedemaker PJ, et al. (1991). Susceptibility to the induction of either autoimmunity or immunosuppression by mercuric chloride is related to the major histocompatibility complex class II haplotype. Eur J Immunol 21:611-616.[Medline] [Order article via Infotrieve]
• Aten J., Veninga A., Coers W., Sonnenberg A., Timpl R., Classen N., et al. (1995). Autoantibodies to the laminin PI fragment in HgCl2-induced membranous glomerulopathy. Am J Pathol 146:1467-1480.[Abstract]
• Berglund A. (1990). Estimation by a 24-hour study of the daily dose of intra-oral mercury vapor inhaled after release from dental amalgam. J Dent Res 69:1646-1651.
• Bernaudin JF, Druet E., Druet P., Masse R. (1981). Inhalation or ingestion of organic or inorganic mercurials produces auto-immune disease in rats. Clin Immunol Immunopathol 20:129-135.[CrossRef][Medline] [Order article via Infotrieve]
• Bigazzi PE (1992). Lessons from animal models: the scope of mercury-induced autoimmunity. Clin Immunol Immunopathol 65:81-84.[CrossRef][Medline] [Order article via Infotrieve]
• Bolewska J., Holmstrup P., Moller-Madsen B., Kenrad B., Danscher G. (1990). Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. J Oral Pathol Med 19:39-42.[CrossRef][Medline] [Order article via Infotrieve]
• Boyd ND, Benediktsson H., Vimy MJ, Hooper DE, Lorscheider FL (1991). Mercury from dental "silver" tooth fillings impairs sheep kidney function. Am J Physiol 261:R1010-R1014.[Medline] [Order article via Infotrieve]
• Clarkson TW (1992). Principles of risk assessment. Adv Dent Res 6:22-27.[Abstract/Free Full Text]
• Clarkson TW, Friberg L., Hursh JB, Nylander M. (1988). The prediction of intake of mercury vapor from amalgam. In: Biological monitoring of toxic metals. Clarkson TW, Friberg L, Nordberg GF, Sager PR, editors. New York: Plenum Press, pp. 247-264.
• Danscher G., Horsted-Bindslev P., Rungby J. (1990). Traces of mercury in organs from primates with amalgam fillings. Exp Mol Pathol 52:291-299.[CrossRef][Medline] [Order article via Infotrieve]
• Drasch G., Schupp I., Riedl G., Giinther G. (1992). Einfluss von Amalgamfullungen auf die Quecksilberkonzentration in menschlichen Organen. Dtsch Zahnärztl 47:409-496.
• Drasch G., Gath HJ, Heissler E., Schupp I., Roider G. (1995). Silver concentration in human tissues. Their dependence on dental amalgam and other factors. J Trace Elements Med Biol 9:82-87.[Medline] [Order article via Infotrieve]
• Druet E., Sapin C., Giinther E., Feingold N., Druet P. (1977). Mercuric chloride-induced anti-glomerular basement membrane antibodies in the rat: genetic control. Eur J Immunol 7:348-351.[Medline] [Order article via Infotrieve]
• Druet P. (1994). Metal-induced autoimmunity. Arch Toxicol 16(Suppl):185-191.
• Druet P., Pelletier L., Rossert J., Druet E., Hirsch F., Sapin C. (1989). Autoimmune reactions induced by metals. In: Autoimmunity and toxicology. Kammuller ME, Bloksma N, Seinens W, editors. Amsterdam: Elsevier, pp. 347-361.
• Eggleston DW, Nylander M. (1987). Correlation of dental amalgam with mercury in brain tissue. J Prosthet Dent 58:704-707.[Medline] [Order article via Infotrieve]
• Eide R., Wesenberg GR (1993). Mercury content of indicators and target organs in rats after long-term, low-level, mercury vapor exposure. Env Res 61:212-222.
• Elinder C-G., Gerhardsson L., Oberdoerster G. (1988). Biological monitoring of toxic metals-overview. In: Biological monitoring of toxic metals. Clarkson TW, Friberg L, Nordberg GF, Sager PR, editors. New York: Plenum Press, pp.1-71.
• Enestrom S., Hultman P. (1995). Does amalgam affect the immune system? A controversial issue. Int Arch Allergy Appl Immunol 106:180-203.
• Eybl V., Koutenska M., Koutensky J., Sykora J., Blehova R., Smolikova V. (1992). Selenium-silver interaction in mice. Arch Toxicol 15(Suppl):160-163.
• Fowler BA, Nordberg GF (1986). Silver. In: Handbook on the toxicology of metals. Friberg L, Nordberg GF, Vouk G, editors. Amsterdam: Elsevier, pp. 521-531.
• Fukatsu A., Brentjens JR, Killen PD, Kleinman HK, Martin GR, Andres GA (1987). Studies on the formation of glomerular immune deposits in Brown Norway rats injected with mercuric chloride. Clin Immunol Immunopathol 45:35-47.[CrossRef][Medline] [Order article via Infotrieve]
• Gross MJ, Harrison JA (1989). Some electrochemical features of the in vivo corrosion of dental amalgams. J Appl Electrochem 19:301-310.
• Hahn LJ, Kloiber R., Vimy MJ, Takahashi Y., Lorscheider FL (1989). Dental "silver" tooth fillings: a source of mercury exposure revealed by whole-body image scan and tissue analysis. FASEB J 3:2641-2646.[Abstract]
• Hahn LJ, Kloiber R., Leininger RW, Vimy MJ, Lorscheider FL (1990). Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues. FASEB J 4:3256-3260.[Abstract]
• Halbach S. (1995). Combined estimation of mercury species released from amalgam. J Dent Res 74:1103-1109.
• Horsted-Bindslev P., Bolewska JE, Arenholt-Bindslev D., Danscher G. (1991a). Dentinal transport of mercury from dental silver amalgam fillings. In: Histo- and cytochemistry as a tool in environmental toxicology. Graumann W, Drukker J, editors. Stuttgart: Fischer Verlag, pp. 321-326.
• Horsted-Bindslev P., Magos L., Holmstrup P., Arenholt-Bindslev D. (1991b). Dental amalgam-A health hazard? Copenhagen: Munksgaard.
• Hua J., Pelletier L., Berlin M., Druet P. (1993). Autoimmune glomerulonephritis induced by mercury vapour exposure in the Brown Norway rat. Toxicology 79:119-129.[CrossRef][Medline] [Order article via Infotrieve]
• Hultman P., Bell LJ, Enestrom S., Pollard KM (1992). Murine susceptibility to mercury. I. Autoantibody profiles and systemic immune deposits in inbred, congenic, and intra-H-2-recombinant strains. Clin Immunol Immunopathol 65:98-109.[CrossRef][Medline] [Order article via Infotrieve]
• Hultman P., Bell LJ, Enestrom S., Pollard KM (1993). Murine susceptibility to mercury. II. Autoantibody profiles and renal immune deposits in hybrid, backcross, and H-2d congenic mice. Clin Immunol Immunopathol 68:9-20.[Medline] [Order article via Infotrieve]
• Hultman P., Enestrom S., Turley SJ, Pollard KM (1994a). Selective induction of anti-fibrillarin autoantibodies by silver nitrate. Clin Exp Immunol 96:285-291.[Medline] [Order article via Infotrieve]
• Hultman P., Johansson U., Turley SJ, Lindh U., Enestrom S., Pollard KM (1994b). Adverse immunological effects and autoimmunity induced by dental amalgam and alloy in mice. FASEB J 8:1183-1190.[Medline] [Order article via Infotrieve]
• Hultman P., Ganowiak K., Turely SJ, Pollard KM (1995). Genetic susceptibility to silver-induced antifibrillarin autoantibodies in mice. Clin Immunol Immunopathol 77:291-297.[Medline] [Order article via Infotrieve]
• Icard P., Pelletier L., Vial MC, Mandet C., Pasquier R., Michel A., et al. (1993). Evidence for a role of antilaminin-producing B cell clones that escape tolerance in the pathogenesis of HgCl2-induced membranous glomerulopathy. Nephrol Dial Transpl 8:122-127.[Abstract/Free Full Text]
• Izui S., Kobayakawa T., Zryd M.-J, Louis J., Lambert P-H. (1977). Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice. II. Correlations between anti-DNA induction and polyclonal antibody formation by various polyclonal B lymphocyte activators. J Immunol 119:2157-2162.[Abstract/Free Full Text]
• Langworth S., Elinder C-G., Akesson A. (1988). Mercury exposure from dental fillings. I. Mercury concentrations in blood and urine. Swed Dent J 12:69-70.[Medline] [Order article via Infotrieve]
• Larsson A., Warfvinge G. (1995). The histopathology of oral mucosa lesions associated with amalgam or porcelain-fused-to-metal restorations. Oral Dis 1:152-158.[Medline] [Order article via Infotrieve]
• Magos L. (1991). Mercury metabolism and toxicology. In: Dental amalgam-a health hazard? Horsted-Bindslev P, Magos L, Holmstrup P, Arenholt-Bindslev D, editors. Copenhagen: Munksgaard, pp. 11-32.
• Masi JV ( 1995). Corrosion of amalgams in restorative materials: the problem and the promise. In: Status quo and perspectives of amalgam and other dental materials. Friberg L, Schrauzers GN, editors. Stuttgart: Thieme Verlag, pp. 120-129.
• Mengel H., Karlog O (1980). Studies on the interaction and distribution of selenite, mercuric, methoxyethyl mercuric and methyl mercuric chloride in rats. I. Analysis of brain, liver, kidney and faeces. Acta Pharmacol Toxicol 46:14-24.[Medline] [Order article via Infotrieve]
• Mirtcheva J., Pfeiffer C., De Bruijn JA, Jaquesmart F., Gleichmann E. (1989). Immunological alterations inducible by mercury compounds. III. H-2A acts as an immune response and H-2E as an immune "suppression" locus for HgCl2-induced antinucleolar auto-antibodies. Eur J Immunol 12:2257-2261.
• Molin C. (1992). Amalgam-fact and fiction. Scand J Dent Res 100:66-73.[Medline] [Order article via Infotrieve]
• Nielsen JB (1992). Toxicokinetics of mercuric chloride and methylmercuric chloride in mice. J Toxicol Environ Hlth 37:85-122.[Medline] [Order article via Infotrieve]
• Nylander M., Friberg L., Lind B. ( 1987). Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. Swed Dent J 11:179-187.[Medline] [Order article via Infotrieve]
• Ogata M., Kenmotsu K., Hirota N., Meguro T., Aikoh H. (1985). Mercury uptake in vivo by normal and acatalasemic mice exposed to metallic mercury vapor (203Hg°) and injected with metallic mercury or mercuric chloride (203HgCl2). Arch Environ Hlth 40:151-154.[Medline] [Order article via Infotrieve]
• Olsson S., Bergman M. (1992). Daily dose calculations from measurements of intra-oral mercury vapor. J Dent Res 71:414-423.
• Sandborgh Englund G., Dahlqvist R., Lindelof B., Soderman E., Jonzon B., Vesterberg O., et al. (1994). DMSA administration to patients with alleged mercury poisoning from dental amalgams: a placebo-controlled study. J Dent Res 73:620-628.
• Sapin C., Hirsh F., Delaporte J-P., Bazin H., Druet P. (1984). Polyclonal IgE increase after HgCl2 injections in BN and LEW rats: a genetic analysis. Immunogenetics 20:227-236.[CrossRef][Medline] [Order article via Infotrieve]
• Schiele R. (1988). Quecksilberabgabe aus Amalgam und Quecksilber-Ablagerung im Organismus und toxikologische Bewertung. In: Amalgam-Pro und Contra. Gutachten-Referate. Knolle G, editor. Koln: Deutscher Arzte-Verlag, pp. 123-131.
• Sellars R., Sellars WA, Taylor RD, Seibert GB (1986). Safety of amalgam: toxicity and allergy. Amalgam survives systemic toxicity challenge. TX Dent J 103:6-12.
• Skare I., Engqvist A. (1994). Human exposure to mercury and silver released from dental amalgam restorations. Arch Environ Hlth 49:384-394.[Medline] [Order article via Infotrieve]
• Warfvinge K., Hua J., Berlin M. (1992). Mercury distribution in the rat brain after mercury vapor exposure. Toxicol Appl Pharmacol 117:46-52.[CrossRef][Medline] [Order article via Infotrieve]
• Warfvinge K., Hansson H., Hultman P. (1995). Systemic autoimmunity due to mercury vapor exposure in genetically susceptible mice: dose-response studies. Toxicol Appl Pharmacol 132:299-309.[CrossRef][Medline] [Order article via Infotrieve]
• Watanabe C., Udono T., Shioiri H., Satoh H. (1993). Change in level of tissue selenium after a single administration of mercuric chloride in mice. Bull Environ Contam Toxicol 51:24-29.[Medline] [Order article via Infotrieve]
• World Health Organization (1991). Inorganic mercury. Environmental Health Criteria 118. Geneva: ICPS.

Journal of Dental Research, Vol. 77, No. 6, 1415-1425 (1998)
DOI: 10.1177/00220345980770060601


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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Hultman, P. Articles by Horsted-Bindslev, P. Search for Related Content PubMed PubMed Citation Articles by Hultman, P. Articles by Horsted-Bindslev, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Autoimmune Diseases Mercury Hazardous Substances DB COPPER, ELEMENTAL MERCURY COMPOUNDS MERCURY, ELEMENTAL SILVER COMPOUNDS SILVER, ELEMENTAL Social Bookmarking                         What's this?