Abstract

Allergic contact dermatitis is mediated in most cases by small molecular substances which are not complete antigens, unlike proteins. According to the concept of the hapten hypothesis derived from the classical studies by Landsteiner, it is generally accepted that small molecules require covalent binding to macro-molecular proteins to become immunogens [1], However, most small molecular compounds are chemically inert and are therefore not able to bind to high molecular proteins by themselves. One possibility is for them to be metabolized to highly reactive species by xenobiotica-metabolizing enzymes [1, 2]. Most xenobiotica are metabolized in the liver. However, the skin has also been recognized to be an important site of extrahepatic metabolism of xenobiotica [3–5]. This is especially the case for the epidermis (the outer layer of the skin), which weighs approximately 225 g and constitutes the major interface between the body and the environment with a surface area of 1.5–2.0 m2 [6, 7]. Immunocompetent cells such as peripheral blood monocytes and lymphocytes have also been shown to possess xenobiotica-metabolizing enzymes [8,9].

Keywords

Hepatitis Glutathione Quinone Carbamazepine Epoxide 

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References

  1. 1.
    Remmer H, Schuppel R (1972) The formation of antigenetic determinants. In: Samter M, Parker CW (eds) International encyclopedia of pharmacology and therapeutics, vol 1. Pergamon, Oxford, p 67Google Scholar
  2. 2.
    Park BK, Pirmohamed M, Kitteringham NR (1995) The role of cytochrome P450 enzymes in hepatic and extrahepatic human drug toxicity. Pharmacol Ther 68:385–424PubMedCrossRefGoogle Scholar
  3. 3.
    Merk HF, Jugert FK, Frankenberg S (1996) Biotransformation in the skin. In: Marzulli FN, Maibach HI (eds) Dermatotoxicology. Taylor and Francis, Washington, pp 61–73Google Scholar
  4. 4.
    Mukhtar H, Ahmad N, Agarwal R (1996) Cytochrome P450 and drug development for skin diseases. Skin Pharmacol 9:231–242PubMedCrossRefGoogle Scholar
  5. 5.
    Vecchini F, Michel S (1994) Importance of cytochrome P450 for the development of new drug concepts in the skin. Eur J Dermatol 4:583–588Google Scholar
  6. 6.
    Eckart RL (1992) The structure and function of the skin. In: Mukhtar H (ed) Pharmacology of the skin. CRC Press, Boca Raton, pp 3–12Google Scholar
  7. 7.Merk HF (1994) Haut. In: Marquardt H, Schäfer SG (eds) Lehrbuch der Toxikologie. Wissenschaftsverlag, Mannheim, pp 271–286Google Scholar
  8. 8.
    Fujino T, Park SS, Gelboin HV (1982) Phenotyping of cytochrome P-450 in human tissue with monoclonal antibodies. Proc Natl Acad Sei USA 79:3682–3686CrossRefGoogle Scholar
  9. 9.
    Merk HF, Baron J, Hertl M, Niederau D, Rübben A (1997) Lymphocyte activation in allergic reactions elicited by small molecular weight compounds. Int Arch Allerg Appl Immunol 113:173–176CrossRefGoogle Scholar
  10. 10.
    Berghard A, Gradin K, Toftgard R (1990) Serum and extracellular calcium modulate induction of cytochrome P-450IA1 in human keratinocytes. J Biol Chem 265:21086–21090PubMedGoogle Scholar
  11. 11.
    Holtzman MJ, Turk J, Pentland A (1989) A regiospecific monooxygenase with novel ste- reopreference is the major pathway for arachidonic acid oxygenation in isolated epidermal cells. J Clin Invest 84:1446–1453PubMedCrossRefGoogle Scholar
  12. 12.
    Khan WA, Das M, Stick S, laved S, Bickers DR, Mukhtar H (1987) Induction of epidermal NAD(P)H: quinone reductase by chemical carcinogens: a possible mechanism for the detoxification. Biochem Biophys Res Commun 146:126PubMedCrossRefGoogle Scholar
  13. 13.
    Coomes MW, Norling AH, Pohl RJ, Muller D, Fouts JR (1983) Foreign compound metabolism by isolated skin cells from hairless mouse. J Pharmacol Exp Ther 225:770–778PubMedGoogle Scholar
  14. 14.
    Guengerich FP, Liebler DC (1985) Encymatic activation of chemicals to toxic metabolites. Crit Rev Toxicol 14:259PubMedCrossRefGoogle Scholar
  15. 15.
    Giralt M, Cervello I, Nogues MR, Puerto AM, Ortin F, Argany N, Mallol J (1996) Glutathione, glutathione -S- transferase, and reactive oxygen species of human scalp sebaceous glands in male pattern baldness. J Invest Dermatol 107:154–158PubMedCrossRefGoogle Scholar
  16. 16.
    Lilienblum W, Irmscher G, Fusenig NE, Bock KW (1986) Induction of UDP-glucuronyl- transferase and arylhydrocarbon hydroxylase activity in mouse skin and in normal and transformed skin cells in culture. Biochem Pharmacol 35:1517PubMedCrossRefGoogle Scholar
  17. 17.
    Merk HF, Jugert FK, Bonnekoh B, Mahrle G (1991) Induction and inhibition of NAD(P)H:quinone reductase in murine and human skin. Skin Pharmacol 4:183–190PubMedCrossRefGoogle Scholar
  18. 18.
    Gonzalez FJ (1990) Molecular genetics of the P-450 superfamiliy. Pharmacol Ther 45:1–38PubMedCrossRefGoogle Scholar
  19. 19.
    Meyer UA (1990) Molecular genetics and the future of pharmacogenetics. Pharmacol Ther 46:349–355PubMedCrossRefGoogle Scholar
  20. 20.
    Nelson DR, Kamataki T, Waxman DJ, et al (1993) The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 12:1–51PubMedCrossRefGoogle Scholar
  21. 21.
    Mukhtar H, Khan IU, Haqqi TM, Bickers DR (1991) Polymerase chain reaction based detection of messenger RNA for three gene families of cytochrome P-450 in mammalian epidermis. J Invest Dermatol 96:581Google Scholar
  22. 22.
    Reiners J J, Amador RC, Pavone A (1990) Modulation of constitutive cytochrome P450 expression in vivo and in vitro in murine keratinocytes as a function of differentiation and extracellular Ca2+ concentration. Proc Natl Acad Sei USA 87:1825–1829CrossRefGoogle Scholar
  23. 23.
    Sadek CM, Allen-Hoffmann BL (1994) Cytochrome P450IA1 is rapidly induced in normal human keratinocytes in the absence of xenobiotics. J Biol Chem 269:16067–16074PubMedGoogle Scholar
  24. 24.
    Nebert DW (1990) Growth signal pathways. Nature 47:709–710CrossRefGoogle Scholar
  25. 25.
    Frankenberg S, Jugert FK, Merk HF (1993) Multiple cytochrome P450 isozymes present in human hair follicle derived keratinocytes. J Invest Dermatol 100:518 [A]Google Scholar
  26. 26.
    Lenoir MC, Bernard BA, Pautrat G, Darmon M, Shroot B (1988) Outer root sheath cells of human hair follicle are able to regenerate a fully differentiated epidermis in vitro. Dev Biol 130:610–620PubMedCrossRefGoogle Scholar
  27. 27.
    Pham MA, Magdalou J, Siest G, Lenoir MC, Bernard BA, Jamoulle JC, Shroot B (1990) Reconstituted epidermis: a novel model for the study of drug metabolism in human epidermis. J Invest Dermatol 94:749–752PubMedCrossRefGoogle Scholar
  28. 28.
    Fischer U, Unruh GE, Dengler HJ (1990) The metabolism of eugenol in man. Xenobiotica 20:209–222PubMedCrossRefGoogle Scholar
  29. 29.
    Mayer RL (1954) Group-sensitization to compounds of quinone structure and its biochemical basis; role of these substances in cancer. Progr Allergy 4:79–172Google Scholar
  30. 30.
    Klemme JC, Mukhtar H, Elmets CA (1987) Induction of contact hypersensitivity to di- methylbenz(a)anthracene and benzo(a)pyrene in C3H/HeN Mice. Cancer Res 47:6074PubMedGoogle Scholar
  31. 31.
    Beaune P, Dansette PM, Mansuy D, Kiffel L, Finck M, Amar C, Leroux JP, Homber JC (1987) Human anti-endoplasmatic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc Natl Acad Sei USA 84:551CrossRefGoogle Scholar
  32. 32.
    Davies GE (1979) Adverse reactions to practolol. In: Turk JL, Parker D (eds) Drugs and immune responsiveness. Macmillan, LondonGoogle Scholar
  33. 33.
    Hertl M, Jugert F, Merk HF (1995) CD8+ dermal T-cells from a sulfamethoxazole-induc- ed bullous exanthem proliferate in response to drug-modified liver microsomes. Br J Dermatol 132:215–220PubMedCrossRefGoogle Scholar
  34. 34.
    Leeder JS, Cannon M, Nakhooda A, Spielberg SP (1988) Drug metabolite toxicity assessed in human lymphocytes with a purified, reconstituted cytochrome P-450 system. J Pharmacol Exp Ther 245:956–962PubMedGoogle Scholar
  35. 35.
    Merk HF, Niederau D, Hertl M, Jugert F (1991) Drug metabolism and drug allergy. In: Ring J, Przybilla B (eds) New trends in allergy, vol III. Springer, Berlin Heidelberg New York, pp 269–280Google Scholar
  36. 36.
    Rieder MJ, Uetrecht J, Shear NH, Cannon M, Miller M, Spielberg SP (1989) Diagnosis of sulfonamide hypersensitivity reactions by in-vitro “rechallenge” with hydroxylamine metabolites. Ann Intern Med 110:286–289PubMedGoogle Scholar
  37. 37.
    Rieder MJ, Uetrecht J, Shear NH, Spielberg SP (1988) Synthesis and in vitro toxicity of hydroxylamine metabolites of sulfonamides. J Pharmacol Exp Ther 244:724–728PubMedGoogle Scholar
  38. 38.
    Shear NH, Spielberg SP, Grant DM, Tang BK, Kalow W (1986) Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Ann Intern Med 105:179–184PubMedGoogle Scholar
  39. 39.
    Benezra C, Sigman CC, Bagheri D, Fraginals R, Maibach HI (1992) Molecular aspects of allergic contact dermatitis. In: Rycroft RJG, Menne T, Frosch PJ, Benezra C (eds) Contact dermatitis. Springer, Berlin Heidelberg New York, pp 103–119Google Scholar
  40. 40.
    Blohm SG, Rajka G (1970) The allergenicity of paraphenylendiamine I. Acta Dermatol Venereol 50:49–50Google Scholar
  41. 41.
    Dobkevitch S, Baer RL (1947) Eczematous cross-hypersensitivity to azodyes in nylon stockings and to paraphenylendiamine. J Invest Dermat 9:203–211Google Scholar
  42. 42.
    Rajka G, Blohm SG (1970) The allergenicity of paraphenylendiamine II. Acta Dermatol Venereol 50:51–54Google Scholar
  43. 43.
    Herve-Bazin B, Gradiski D, Duprat P, Marignac B, Foussereau J, Cavelier C, Bieber P (1977) Occupational eczema from N-isopropyl-N’-phenyl-paraphenylenediamine (IPPD) and N-dimethyl-1,3 butyl-N’-phenylparaphenylenediamine (DMPPD) in tyres. Contact Dermatitis 3:1CrossRefGoogle Scholar
  44. 44.
    Baer RL, Leider M, Mayer RL (1948) Possible eczematous cross-hypersensitivity between paraphenylenediamine and azo-dyes certified for use in foods, drugs and cosmetics. Proc Soc Exp Biol 67:489–494PubMedGoogle Scholar
  45. 45.
    Mayer RL (1958) Die Beziehung zwischen toxischen, allergischen und carcinogenen Eigenschaften aromatischer Amine. Gruppenempfindlichkeit gegen Körper von Chinonstruktur. Klin Wochenschr 36:885–893PubMedCrossRefGoogle Scholar
  46. 46.
    Meitzer L, Baer RL (1949) Sensitization to monoglycerol para-aminobenzoate. J Invest Dermat 12:31–39Google Scholar
  47. 47.
    Sulzberger MB, Kanof A, Baer RL, Lowenberg C (1943) Sensitization by topical application of sulfonamides. J Allergy 18:92–103CrossRefGoogle Scholar
  48. 48.
    Ames BN, Kämmen HO, Yamasaki E (1975) Hair dyes are mutagenic: identification of a variety of mutagenic ingredients. Proc Natl Acad Sei USA 72:2423–2427CrossRefGoogle Scholar
  49. 49.
    Blijleven WGH (1977) Mutagenicity of four hair dyes in drosophila melanogaster. Mutat Res 48:181–186PubMedCrossRefGoogle Scholar
  50. 50.
    Wilkinson DS, Fregert S, Magnusson B, Bandmann HJ, Calnan CD, Cronin E, Hjorth N, Maibach HJ, Malten KE, Meneghini CL, Pirila V (1970) Terminology of contact dermatitis. Acta Dermatol Venereol 50:2871Google Scholar
  51. 51.
    Merk H, Mukhtar H, Kaufmann I, Das M, Bickers DR (1987) Human hair follicle benzo(a)pyrene and benzo(a)pyrene 7,8-diol metabolism: effect of exposure to a coal tar-containing shampoo. J Invest Dermatol 88:71–76PubMedCrossRefGoogle Scholar
  52. 52.
    Basketter DA, Pendlington RU, Sarll A, Scholes E (1996) The role of P450 1A in the activation of prohaptens in skin sensitization. J Invest Dermatol 106:915 (abstr)Google Scholar
  53. 53.
    Vecchini F, Mace K, Magdalou J, Mahe Y, Bernard BA, Shroot B (1995) Constitutive and inducible expression of drug metabolizing enzymes in cultured human keratinocytes. Br J Dermatol 132:14–21PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Hans F. Merk

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