Porphyria Caused by Hexachlorobenzene and Other Polyhalogenated Aromatic Hydrocarbons

  • G. H. Elder
Part of the Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology book series (HEP, volume 44)


The polyhalogenated aromatic hydrocarbons which cause the specific form of hepatic porphyria described in this Chapter are shown in Figure 1. Prolonged administration of these compounds to susceptible mammals and birds leads to the development, after a delay which varies between species but is usually at least a week, of massive overproduction of uroporphyrin and heptacarboxyhc porphyrin and, to a lesser extent, porphyrins with 6, 5 and 4 carboxyl groups.


Iron Overload Japanese Quail Smooth Endoplasmic Reticulum Porphyria Cutanea Tarda Hepatic Porphyria 
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  1. Abbott, D.C., Collins, G.B., Goulding, R.: Organochlorine pesticide residues in human fat in the United Kingdom 1969–1971. Brit. med. J. 1972 II, 553–556Google Scholar
  2. Alvares, A.P., Bickers, D.R., Kappas, A.: Polychlorinated biphenyls: a new type of inducer of cytochrome P-448 in the liver. Proc. nat. Acad. Sci. (Wash.) 70, 1321–1325 (1973)Google Scholar
  3. Bach, P.H., Taljaard, J.J.F., Joubert, S.M., Shanley, B.C.: The effect of iron overload on the development of hexachlorobenzene (HCB) porphyria. S. Afr. J. Lab. clin. Med. 17, 75–76 (1971)Google Scholar
  4. Baptista de Almeida, J.A.P., Kenner, G.W., Smith, K.M., Sutton, M.J.: A stepwise synthesis of unsymmetrically substituted porphyrins: isocoproporphyrin. J. C. S. Chem. Commun., 111–112 (1975)Google Scholar
  5. Battle, A.M. del C., Grinstein, M.: Porphyrin biosynthesis.II Phyriaporphyrinogen III, a normal intermediate in the biosynthesis of protoporphyrin IX. Biochim. biophys. Acta (Amst.) 82, 13–20 (1964)Google Scholar
  6. Bleiberg, J., Wallen, M., Brodkin, R., Applebaum, I.L.: Industrially-acquired porphyria. Arch. Derm. (Chic.) 89, 793–797 (1964)Google Scholar
  7. Brady, M.N., Siyali, D.S.: Hexachlorobenzene in human body fat. Med. J. Aust. 1, 158–161 (1972)PubMedGoogle Scholar
  8. Bruckner, J.V., Khanna, K.L., Cornish, H.H.: Effect of chronic ingestion of polychlorinated biphenyls on the rat. Toxicol, appl. Pharmacol. 29, 103 (1974)Google Scholar
  9. Burnett, J., Pathak, M.: Effect of light upon porphyrin metabolism of rats. Arch. Derm. (Chic.) 89, 257–266 (1964)Google Scholar
  10. Burse, V.M., Kimbrough, R.D., Villeneuva, E.C., Jennins, R.W., Linder, R.E., Sovocool, G.W.: Polychlorinated biphenyls. Arch, environm. Hlth. 29, 301–307 (1974)Google Scholar
  11. Cam, C.: Hexachlorobenzen ile muzmin zehirlenmeye bagli deri porfirisi vakalari. Sagl. Derg. 32, 215–216 (1958)Google Scholar
  12. Cam, C.: Intoksikasyona bagli deri porfirilevi. Dirim 34, 11 (1959)Google Scholar
  13. Cam, C.: A new epidemic dermatosis of children. Ann. Derm. Syph. (Paris) 87, 393–397 (1960)Google Scholar
  14. Cam, C., Nigogosyan, G.: Acquired toxic porphyria cutanea tarda due to hexachlorobenzene. J. Amer. med. Ass. 183, 88–91 (1963)Google Scholar
  15. Cameron, G.R., Thomas, J.C., Ashmore, S.A., Buchan, J.L., Warren, E.H., Hughes, A.W.McK.: The toxicity of certain chlorine derivatives of benzene, with special reference to O-dichlorobenzene. J. Path. Bact. 44, 281–296 (1937)Google Scholar
  16. Campbell, J.A.H.: Pathological aspects of hexachlorobenzene feeding in rats. S. Afr. J. Lab. clin. Med. 9, 203–206 (1963)Google Scholar
  17. Cetingil, A.I., Özen, M.A.: Toxic porphyria. Blood 16, 1002–1011 (1960)PubMedGoogle Scholar
  18. Chu, T.C., Chu, E.J.-H.: Porphyrin patterns in different types of porphyria. Clin. Chem. 13, 371–387 (1967)PubMedGoogle Scholar
  19. Conney, A.H.: Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317–366 (1967)PubMedGoogle Scholar
  20. Crow, K.D.: Chloracne. Trans. St. John’s Hosp. derm. Soc. (Lond.) 56, 79–99 (1970)Google Scholar
  21. Dean, G.: The Porphyrias: A Story of Inheritance and Environment, 2nd ed. London: Pitman Medical Publishing 1971Google Scholar
  22. De Matteis, F.: Disturbances of liver porphyrin metabolism caused by drugs. Pharmacol. Rev. 19, 523–557 (1967)PubMedGoogle Scholar
  23. De Matteis, F.: Toxic hepatic porphyrias. Sem. Haematol. 5, 409–423 (1968)Google Scholar
  24. De Matteis, F.: Iron-dependent degradation of liver heme in vivo. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 37–42. Basel: Karger 1976Google Scholar
  25. De Matteis, F., Prior, B.E., Rimington, C.: Nervous and biochemical disturbances following hexachlorobenzene intoxication. Nature (Lond.) 191, 363–366 (1961)Google Scholar
  26. De Matteis, F., Sparks, R.G.: Iron-dependent loss of liver cytochrome P-450 heme in vivo and in vitro. FEBS Lett. 141–143 (1973)Google Scholar
  27. Dogramaci, I., Kenanoglu, A., Muftu, Y., Ergene, T., Wray, J.D.: Bone and joint changes in patients with porphyria turcica. Turk. J. Pediat. 4, 149–156 (1962b)Google Scholar
  28. Dogramaci, I., Tinaztepe, B., Gunalp, A.: Condition of the liver in patients with toxic cutaneous porphyria. Turk. J. Pediat. 4, 103–106 (1962c)Google Scholar
  29. Dogramaci, I., Wray, J.D., Ergene, T., Sezer, V., Muftu, Y.: Porphyria turcica, a survey of 592 cases of cutaneous porphyria seen in southeastern Turkey. Turk. J. Pediat. 4, 138–147 (1962a)Google Scholar
  30. Doss, M., Meinhof, W., Look, D., Henning, H., Nawrocki, P., Dolle, W., Strohmeyer, G., Filippini, L.: Porphyrins in liver and urine in acute intermittent and chronic hepatic porphyrias. S. Afr. J. Lab. clin. Med. 17, 50–54 (1971)Google Scholar
  31. Doss, M., Schermuly, E., Koss, G.: Hexachlorobenzene porphyria in rats as a model for human chronic hepatic porphyrias. Ann. Clin. Res. 8, Suppl. 17, 171–181 (1976)PubMedGoogle Scholar
  32. Dowdle, E., Goldswain, P., Spong, N., Eales, L.: The pattern of porphyrin isomer accumulation and excretion in symptomatic porphyria. Clin. Sci. 39, 147–158 (1970)PubMedGoogle Scholar
  33. Elder, G.H.: Identification of a group of tetracarboxylate porphyrins, containing one acetate and three propionate β-substituents, in faeces from patients with symptomatic cutaneous hepatic porphyria and from rats with porphyria due to hexachlorobenzene. Biochem. J. 126, 877–891 (1972)PubMedGoogle Scholar
  34. Elder, G.H.: The porphyrin excretion pattern of symptomatic cutaneous hepatic porphyria. M.D. Thesis, University of Cambridge, 1973Google Scholar
  35. Elder, G.H.: The metabolism of porphyrins of the isocoproporphyrin series. Enzyme 17, 61–68 (1974)PubMedGoogle Scholar
  36. Elder, G.H.: The differentiation of porphyria cutanea tarda symptomatica from other types of porphyria by the measurement of isocoproporphyrin in faeces. J. clin. Path. 28, 601–607 (1975)PubMedGoogle Scholar
  37. Elder, G.H., Evans, J.O., Matlin, S.: The porphyrogenic action of polychlorinated hydrocarbons. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 424–431. Basel: Karger 1976aGoogle Scholar
  38. Elder, G.H., Evans, J. O., Matlin, S.: The effect of the porphyrogenic compound, hexachlorobenzene, on the activity of uroporphyrinogen decarboxylase in rat liver. Clin. Sci. molec. Med. 51, 71–80 (1976b)Google Scholar
  39. Elder, G.H., Nicholson, D.C, Gray, C.H.: The porphyrias: a review. J. clin. Path. 25, 1013–1033 (1972)PubMedGoogle Scholar
  40. Farber, T.M., Baker, A.: Microsomal enzyme induction by hexabromobiphenyl. Toxicol, appl. Pharmacol. 29, 102 Abstr. No. 68 (1974)Google Scholar
  41. Fishbein, L.: Toxicity of chlorinated biphenyls. Ann. Rev. Pharmacol. 14, 139–156 (1974)Google Scholar
  42. Gajdos, A., Gajdos-Török, M.: The therapeutic effect of adenosine-5-monophosphoric acid in porphyria. Lancet 1961 II, 175–177Google Scholar
  43. Garcia, D.C., San Martin de Viale, L.L., Tomio, J.M., Grinstein, M.: Porphyrin biosynthesis. X. Porphyrinogen carboxy-lyase from avian erythrocytes: further properties. Biochim. biophys. Acta (Amst.) 309, 203–210 (1973)PubMedGoogle Scholar
  44. Goldstein, J.A., Hickman, P., Bergman, H., Vos, J.G.: Hepatic porphyria induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse. Res. Commun. chem. Path. Pharmacol. 6, 919–928 (1973)Google Scholar
  45. Goldstein, J.A., Hickman, P., Jue, D.L.: Experimental hepatic porphyria induced by polychlorinated biphenyls. Toxicol, appl. Pharmacol. 27, 437–448 (1974)Google Scholar
  46. Gombos, B., Pechanova, A., Koziak, B., Moscovicova, E.: Porphyria cutanea tarda and acne chlorina at the production of cyclic chlorinated hydrocarbons. Bratisl. lek. Listy 51, 640 (1969)PubMedGoogle Scholar
  47. Granick, S.: The induction in vitro of the synthesis of δ ALA synthetase in chemical porphyria: a response to certain drugs, sex hormones and foreign chemicals. J. biol. Chem. 24, 1359–1375 (1966)Google Scholar
  48. Grant, D.L., Iverson, F., Hatina, G.V., Villeneuve, D.C.: Effects of hexachlorobenzene on liver porphyrin levels and microsomal enzymes in the rat. Environ. Physiol. Biochem. 4, 159–165 (1974)PubMedGoogle Scholar
  49. Greig, J.B.: Effect of 2,3,7,8-tetrachlorodibenzo-l,4-dioxin on drug metabolism in the rat. Biochem. Pharmacol. 21, 3196–3198 (1972)PubMedGoogle Scholar
  50. Greig, J.B., De Matteis, F.: Effects of 2,3,7,8-tetrachlorodibenzo-1,4-dioxin on drug metabolism and hepatic microsomes of rats and mice. Environ. Hlth. Perspect. 5, 211–219 (1973)Google Scholar
  51. Hansell, M.M., Ecobichon, D.J.: Effects of chemically pure biphenyls on the morphology of rat liver. Toxicol. appl. Pharmacol. 28, 418–427 (1974)PubMedGoogle Scholar
  52. Heikel, T., Lockwood, W.H., Rimington, C.: Formation of non-enzymic heme. Nature (Lond.) 182, 313 (1958)Google Scholar
  53. Hershko, Ch., Eilon, L.: The effect of sex difference on iron exchange in the rat. Brit. J. Haemat. 28, 471–482 (1974)PubMedGoogle Scholar
  54. Hutterer, F., Schaffner, F., Klion, F.M., Popper, H.: Hypertrophic, hypoactive smooth endoplasmic reticulum: A sensitive indicator of hepatotoxicity exemplified by dieldrin. Science 161, 1017–1019 (1968).PubMedGoogle Scholar
  55. Hutzinger, O., Nash, D.M., Safe, S., Defreitas, A.S.W., Norstrom, R.J., Wildish, D.J., Zitko, V.: Polychlorinated biphenyls: metabolic behaviour of pure isomers in pigeons, rats and brook trout. Science 178, 312–314 (1972)PubMedGoogle Scholar
  56. Ippen, H., Aust, D.: Klinisch-experimentelle Untersuchungen zur Entstehung der Porphyrien. I. Allgemeine und tierexperimentelle Modellversuche. Arch. Derm. Forsch. 245, 110–124 (1972)Google Scholar
  57. Ippen, H., Aust, D., Goerz, G.: Klinisch-experimentelle Untersuchungen zur Entstehung der Porphyrien. III. Wirkung einiger Steroid-Hormone auf die “latente Hexachlorobenzol-Porphyrie” der Ratte. Arch. Derm. Forsch. 245, 305–317 (1972a)Google Scholar
  58. Ippen, H., Hüttenhain, S., Aust, D.: Klinisch-experimentelle Untersuchungen zur Entstehung der Porphyrien. II. Wirkung von Äthylalkohol auf die Hexachlorobenzol-Porphyrie der Ratte. Arch. Derm. Forsch. 245, 191–202 (1972b)Google Scholar
  59. Jackson, A.H., Sancovich, H.A., Ferramola, A.M., Evans, N., Games, D.E., Matlin, S.A., Eider, G.H., Smith, S.G.: Macrocyclic intermediates in the biosynthesis of porphyrins. Phil. Trans. B 273, 191–206 (1976)Google Scholar
  60. Jensen, S., Sundstrom, G.: Metabolic hydroxylation of a chlorobiphenyl containing only isolated unsubstituted positions — 2,2′,4,4′,5,5′-hexachlorobiphenyl. Nature (Lond.) 251, 219–220 (1974)PubMedGoogle Scholar
  61. Jirásek, L., Kalensky, J., Kubec, K.: Acne chlorina, porphyria cutanea tarda pri výrobě herbicid. Čsl. Derm. 48, 306–317 (1973)Google Scholar
  62. Jirásek, L., Kalenský, J., Kubec, K., Pazderová, J., Lukáš, E.: Acne chlorina, porphyria cutanea tarda a jiné projevy celkové intoxikace pri výrobě herbicid. II. Čsl. Derm. 49, 145–157 (1974)Google Scholar
  63. Johnstone, G.J., Ecobichon, D.J., Hutzinger, O.: The influence of pure polychlorinated biphenyl compounds on hepatic function in the rat. Toxicol, appl. Pharmacol. 28, 66–81 (1974)Google Scholar
  64. Jones, G., Butler, W.H.: A morphological study of the liver lesion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. J. Path. 112, 93–98 (1974)PubMedGoogle Scholar
  65. Joubert, S.M., Taljaard, J.J.F., Shanley, B.C.: Aetiological relationship between hepatic siderosis and symptomatic porphyria cutanea tarda. Enzyme 16, 305–313 (1973)PubMedGoogle Scholar
  66. Kalivas, J.: Urinary clues to the pathogenesis of porphyria cutanea tarda. Clin. Biochem. 2, 417–421 (1969)Google Scholar
  67. Kalivas, J.T., Pathak, M.A., Fitzpatrick, T.B.: Phlebotomy and iron overload in porphyria cutanea tarda. Lancet 1969 I, 1184–1187Google Scholar
  68. Kantemir, I.: Porphyrin kimyasi ve analiz metodlari. Turk Ij. tecr. Biyol. Derg. 20, 1 (1960)Google Scholar
  69. Kimbrough, R.D.: The toxicity of polychlorinated polycyclic compounds and related chemicals. CRC Crit. Rev. Toxicol. 2, 445–498 (1974)PubMedGoogle Scholar
  70. Kimbrough, R.D., Linder, R.E., Gaines, T.B.: Morphological changes in livers of rats fed polychlorinated biphenyls. Arch, environm. Hlth. 25, 354–365 (1972)Google Scholar
  71. Koeman, J.H., Noever de Brauw, M.C., Vos, R.H.: Chlorinated biphenyls in fish, mussels and birds from the river Rhine and the Netherlands coastal area. Nature (Lond.) 221, 1126–1128 (1969)PubMedGoogle Scholar
  72. Koss, G.: Studies on the pharmacokinetics of hexachlorobenzene in rats. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 414–417. Basel: Karger 1976Google Scholar
  73. Kuiper-Goodman, T., Grant, D., Korsrod, G., Moodie, C.A., Munro, I.C.: Toxic effects of hexachlorobenzene in the rat: correlations of electron microscopy with other toxic parameters. Toxicol, appl. Pharmacol. 29, 101 Abstr. 67 (1974)Google Scholar
  74. Kushner, J.P., Barbuto, A.J.: Decreased activity of hepatic uroporphyrinogen decarboxylase (urodecarb) in porphyria cutanea tarda (PCT). Clin. Res. 22, 178 (1974)Google Scholar
  75. Kushner, J.P., Barbuto, A.J.: An inherited defect in porphyria cutanea tarda (PCT): decreased uroporphyrinogen decarboxylase. Clin. Res. 23, 403 (1975a)Google Scholar
  76. Kushner, J.P., Lee, G.R., Nacht, S.: The role of iron in the pathogenesis of porphyria cutanea tarda: an in vitro model. J. clin. Invest. 51, 3044–3051 (1972)PubMedGoogle Scholar
  77. Kushner, J.P., Steinmuller, D.P., Lee, G.R.: Inhibition of uroporphyrinogen decarboxylase activity by iron. Clin. Res. 21, 266 (1973)Google Scholar
  78. Kushner, J.P., Steinmuller, D.P., Lee, G.R.: The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase. J. clin. Invest. 56, 661–667 (1975b)PubMedGoogle Scholar
  79. Lucier, G.W., McDaniel, O.S., Hook, G.E.R., Fowler, B.A., Sonawane, B.R., Faeder, E.: TCDD-induced changes in rat liver microsomal enzymes. Environ. Hlth. Perspect. 5, 199–209 (1973)Google Scholar
  80. Lui, H., Sweeney, G.D.: Hepatic metabolism of hexachlorobenzene in rats. Febs Lett. 51, 225–226 (1975)PubMedGoogle Scholar
  81. Lui, H., Sampson, R., Sweeney, G.D.: Hexachlorobenzene porphyria: purity and metabolic fate of hexachlorobenzene. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 405–413. Basel: Karger 1976Google Scholar
  82. Lundvall, O.: The effect of phlebotomy therapy in porphyria cutanea tarda. Its relation to the phlebotomy induced reduction of iron stores. Acta. med. scard. 189, 33–50 (1971a)Google Scholar
  83. Lundvall, O.: The effect of replenishment of iron stores after phlebotomy therapy in porphyria cutanea tarda. Acta med. scand. 189, 51–63 (1971b)PubMedGoogle Scholar
  84. Lundvall, O., Enerback, L.: Hepatic fluorescence in porphyria cutanea tarda studied in fine needle aspiration biopsy smears. J. clin. Path. 22, 704–709 (1969)PubMedGoogle Scholar
  85. Marver, H.S., Schmid, R.: The porphyrias. In: The Metabolic Basis of Inherited Disease. 3rd ed. New York: McGraw-Hill 1972Google Scholar
  86. Mauzerall, D., Granick, S.: Porphyrin biosynthesis in erythrocytes. II. Uroporphyrinogen and its decarboxylase. J. biol. Chem. 232, 1141–1161 (1958)PubMedGoogle Scholar
  87. May, G.: Chloracne from the accidental production of tetrachlorodibenzodioxin. Brit. J.Industr. Med. 30, 276–283 (1973)PubMedGoogle Scholar
  88. Medline, A., Bain, E., Menon, A.I., Haberman, H.F.: Hexachlorobenzene and rat liver. Arch. Path. (Chic.) 96, 61–65 (1973)Google Scholar
  89. Meyer, U.A., Marver, H.S.: Enhancement of the fractional catabolic rate of microsomal heme in chemically induced porphyria. S. Afr. J. Lab. clin. Med. 17, 175–177 (1971)Google Scholar
  90. Milnes, M.H.: Formation of 2,3,7,8-tetrachlorodibenzodioxin by thermal decomposition of 2,4,5-trichlorophenate. Nature (Lond.) 232, 395–396 (1971)PubMedGoogle Scholar
  91. Moore, M.R., Battistini, V., Beattie, A.D., Goldberg, A.: The effect of certain barbiturates on the hepatic porphyrin metabolism of rats. Biochem. Pharmacol. 19, 751–757 (1970)PubMedGoogle Scholar
  92. Moore, M.R., Turnbull, A.L., Barnado, D., Beattie, A.D., Magnus, I.A., Goldberg, A.: Hepatic δ-aminolaevulinic acid synthetase activity in porphyria cutanea tarda. Lancet 1972 II, 97–100Google Scholar
  93. Morley, A., Geary, D., Harben, F.: Hexachlorobenzene pesticides and porphyria. Med. J. Aust. 1, 565 (1973)PubMedGoogle Scholar
  94. Nakao, K., Wada, O., Takaku, F., Sassa, S., Yano, Y., Urata, G.: The origin of the increased protoporphyrin in erythrocytes of mice with experimentally induced porphyria. J. Lab. clin. Med. 70, 923–932 (1967)PubMedGoogle Scholar
  95. Ockner, R.K., Schmid, R.: Acquired porphyria in man and rat due to hexachlorobenzene intoxication. Nature (Lond.) 189, 499 (1961)PubMedGoogle Scholar
  96. Parke, D.V., Williams, R.T.: Studies in detoxication. 81. The metabolism of halogenobenzenes: (a) Penta- and hexa-chlorobenzenes (b) Further observations on 1:3:5-trichlorobenzene. Biochem. J. 74, 5–9 (1960)PubMedGoogle Scholar
  97. Pearson, R.W., Malkinson, F.D.: Some observations on hexachlorobenzene induced experimental porphyria. J. invest. Derm. 44, 420–432 (1965)PubMedGoogle Scholar
  98. Perez, V., Schaffner, F., Popper, H.: Hepatic drug reactions. In: Progress in Liver Diseases, Vol. 4. London — New York: Grune and Stratton 1972Google Scholar
  99. Peters, H.A., Johnson, S.A.M., Cam, S., Oral, S., Müftü, Y., Ergene, T.: Hexachlorobenzene-induced porphyria: effect of chelation of the disease, porphyrin and metal metabolism. Amer. J. med. Sci. 251, 314–322 (1966)PubMedGoogle Scholar
  100. Pimstone, N.R., Blekkenhorst, G., Eales, L.: Enzymatic defects in hepatic porphyria: preliminary observations in patients with porphyria cutanea tarda and variegate porphyria. Enzyme 16, 354–366 (1973)PubMedGoogle Scholar
  101. Piper, W.N., Rose, J.Q., Gehring, P.J.: Excretion and tissue distribution of 2,3,7,8-tetrachloro-dibenzo-p-dioxin in the rat. Environ. Hlth. Perspect. 5, 241–244 (1973)Google Scholar
  102. Poland, A., Glover, E.: 2,3,7,8-tetrachlorodibenzo-p-dioxin: a potent inducer of 5-aminolevulinic acid synthetase. Science 179, 476–477 (1973a)PubMedGoogle Scholar
  103. Poland, A., Glover, E.: Studies on the mechanism of toxicity of the chlorinated dibenzo-p-dioxins. Environ. Hlth. Perspect. 5, 245–251 (1973b)Google Scholar
  104. Poland, A., Goldstein, J., Hickman, P., Burse, V.W.: A reciprocal relationship between the induction of δ-aminolevulinic acid synthetase and drug metabolism produced by m-dichlorobenzene. Biochem. Pharmacol. 20, 1281–1290 (1971b)PubMedGoogle Scholar
  105. Poland, A.P., Smith, D., Metter, G., Possick, P.: A health survey of workers in a 2,4-D and 2,4,5-T plant. Arch. environm. Hlth. 22, 316–327 (1971a)Google Scholar
  106. Rajamanickam, C., Amrutavalli, J., Rao, M.R.S., Padmanaban, G.: Effect of hexachlorobenzene on heme synthesis. Biochem. J. 129, 381–387 (1972)PubMedGoogle Scholar
  107. Ramsay, CA., Magnus, I.A., Turnbull, A., Baker, H.: The treatment of porphyria cutanea tarda by venesection. Quart. J. med. N.S. 43, 1–24 (1974)Google Scholar
  108. Rimington, C.: Patterns of porphyrin excretion and their interpretation. S. Afr. J. Lab. clin. Med. 9, 255–261 (1963)Google Scholar
  109. Rimington, C., Ziegler, G.: Experimental porphyria in rats induced by chlorinated benzenes. Biochem. Pharmacol. 12, 1387–1397 (1963)PubMedGoogle Scholar
  110. Romeo, G., Levin, E.Y.: Uroporphyrinogen decarboxylase from mouse spleen. Biochim. biophys. Acta (Amst.) 230, 330–341 (1971)PubMedGoogle Scholar
  111. Ryan, D., Lu, A.Y.H., West, S., Levin, W.: Multiple forms of cytochrome P-450 in phenobarbital and 3-methylcholanthrene-treated rats. Separation and spectral properties. J. biol. Chem. 250, 2157–2163 (1975)PubMedGoogle Scholar
  112. San Martin de Viale, L.C., Grinstein, M.: Porphyrin biosynthesis. IV. 5- and 6-COOH porphyrinogens (type III) as normal intermediates in heme biosynthesis. Biochim. biophys. Acta (Amst.) 158, 79–91 (1968)Google Scholar
  113. San Martin de Viale, L.C., Rios de Molina, M. del C., Wainstock de Calmanovici, R., Tomio, J.M.: Experimental porphyria produced in rats by hexachlorobenzene IV. Studies on the stepwise decarboxylation of uroporphyrinogen and phyriaporphyrinogen ‘in vivo’ and ‘in vitro’ in several tissues. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 445–452. Basel: Karger 1976bGoogle Scholar
  114. San Martin de Viale, L.C., Russo, M.C., Rios de Molina, M. del C., Grinstein, M.: Experimental porphyria induced in rats by hexachlorobenzene II. The effect of oestradiol-17β. Abstracts of 1st International Porphyrin Meeting, Freiburg, (1976a)Google Scholar
  115. San Martin de Viale, L.C., Tomio, J.M., Ferramola, A.M., Sancovich, H.A., Tigier, H.A.: Nat. Meeting Arg. Soc. biochem. Invest. Abstr. 8 (1972)Google Scholar
  116. San Martin de Viale, L.C., Tomio, J.M., Ferramola, A.M., Sancovich, H.A., Tigier, H.A.: Experimental porphyria induced in rats by hexachlorobenzene III. Studies on enzymes associated with heme pathway—the effect of oestradiol-17β. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 453–458. Basel: Karger 1976cGoogle Scholar
  117. San Martin de Viale, L.C., Viale, A.A., Nacht, S., Grinstein, M.: Experimental porphyria induced in rats by hexachlorobenzene. A study of the porphyrins excreted by urine. Clin. chim. Acta 28, 13–25 (1970)PubMedGoogle Scholar
  118. Saunders, S.J., Williams, J., Levey, M.: Iron metabolism in symptomatic porphyria. S. Afr. J. Lab. clin. Med. 9, 277–282 (1963)Google Scholar
  119. Schmid, R.: Cutaneous porphyria in Turkey. New Engl. J. Med. 263, 397–398 (1960)PubMedGoogle Scholar
  120. Shanley, B.C., Zail, S.S., Joubert, S.M.: Porphyrin metabolism in experimental hepatic siderosis in the rat. Brit. J. Haemat. 18, 79–87 (1970)PubMedGoogle Scholar
  121. Simon, N., Dobozy, A., Berko, G.: Porphyrinstoffwechsel und klinisch-laboratorium-mäßige Untersuchungen in Modellversuchen und an Patienten mit Porphyria cutanea tarda. Arch. klin. exp. Derm. 238, 38–43 (1970)PubMedGoogle Scholar
  122. Simon, N., Siklosi, C.: Experimentelles Porphyrie-Modell mit Hexachlor-Cyclohexan. Z. Hautkr. 49, 497–504 (1974)PubMedGoogle Scholar
  123. Simon, N., Siklosi, C., Koszo, F.: The role of damages in cellular membrane structures in the development of phorphyria cutanea tarda. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 432–437. Basel: Karger 1976Google Scholar
  124. Sinclair, P.R., Granick, S.: Uroporphyrin formation induced by chlorinated hydrocarbons (lindane, polychlorinated biphenyls, tetrachlorodibenzo-p-dioxin): requirements for endogenous iron, protein synthesis and drug-metabolising activity. Biochem. biophys. Res. Commun. 61, 124–133 (1974)PubMedGoogle Scholar
  125. Siyali, D.S.: Hexachlorobenzene and other organochlorine pesticides in human blood. Med. J. Aust. 2, 1063–1066 (1972)PubMedGoogle Scholar
  126. Slater, T.F., Ziegler, G.: Nicotinamide adenine dinucleotides in the liver in experimentally induced porphyrias. Biochem. Pharmacol. 15, 1279–1285 (1966)Google Scholar
  127. Stoll, M., Elder, G.H., Games, D.E., O’Hanlon, P., Millington, D.S., Jackson, A.H.: Isocoproporphyrin: Nuclear-magnetic-resonance and mass-spectral methods for the determination of porphyrin structure. Biochem. J. 131, 429–432 (1973)PubMedGoogle Scholar
  128. Stonard, M.D.: Experimental hepatic porphyria induced by hexachlorobenzene as a model for human symptomatic porphyria. Brit. J. Haemat. 27, 617–125 (1974)PubMedGoogle Scholar
  129. Stonard, M.D.: Mixed type hepatic microsomal enzyme induction by hexachlorobenzene. Biochem. Pharmacol. 24, 1959–1963 (1975)PubMedGoogle Scholar
  130. Stonard, M.D.: Abstracts of 1st International Porphyrin Meeting, Freiburg 1976Google Scholar
  131. Stonard, M.D., Nenov, P.Z.: Effect of HCB on hepatic microsomal enzymes in the rat. Biochem. Pharmacol. 23, 2175–2184 (1974)PubMedGoogle Scholar
  132. Strik, J.J.T.W.A.: Toxicity of hexachlorobenzene (HCB) and hexabromobiphenyl (HBB). Meded. Fak. Landbouwweten-Schappen, Gent, 38, 709–716 (1973a)Google Scholar
  133. Strik, J.J.T.W.A.: Chemical porphyria in Japanese Quail (Coturnix c. Japonica). Enzyme 16, 211–223 (1973b)PubMedGoogle Scholar
  134. Strik, J.J.T.W.A.: Species differences in experimental porphyria caused by polyhalogenated aromatic compounds. Enzyme 16, 224–228 (1973c)PubMedGoogle Scholar
  135. Strik, J.J.T.W.A., Koeman, J.H.: Porphyrinogenic action of hexachlorobenzene and octachlorostyrene. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 418–423. Basel: Karger 1976Google Scholar
  136. Strik, J.J.T.W.A., Wit, J.G.: Hepatic porphyria in birds and mammals. TNO-nieuws 27, 604–610 (1972)Google Scholar
  137. Sweeney, G.D.: Hepatic catalase activity during states of altered heme synthesis. In: Porphyrins in Human Diseases. Doss, M. (ed.), pp. 53–61. Basel: Karger 1976Google Scholar
  138. Sweeney, G.D., Janigan, D., Mayman, D., Lai, H.: The experimental prophyrias—a group of distinctive metabolic lesions. S. Afr. J. Lab. clin. Med. 17, 68–72 (1971)Google Scholar
  139. Taljaard, J.J.F., Shanley, B.C., Deppe, W.M., Joubert, S.M.: Porphyrin metabolism in experimental hepatic siderosis in the rat. II. Combined effect of iron overload and hexachlorobenzene. Brit. J. Haemat. 23, 513–519 (1972a)PubMedGoogle Scholar
  140. Taljaard, J.J.F., Shanley, B.C., Deppe, W.M., Joubert, S.M.: Porphyrin metabolism in experimental hepatic siderosis in the rat. III. Effect of iron overload and hexachlorobenzene on liver heme biosynthesis. Brit. J. Haemat. 23, 587–593 (1972b)PubMedGoogle Scholar
  141. Taljaard, J.J.F., Shanley, B.C., Joubert, S.M.: Decreased uroporphyrinogen decarboxylase activity in “experimental symptomatic porphyria”. Life Sci. 10, 887–893 (1971)Google Scholar
  142. Taljaard, J.J.F., Shanley, B.C., Joubert, S.M., Deppe, W.M.: Incorporation of (4–14C) 8-amino-laevulinate into urinary porphyrins in porphyria cutanea tarda: effect of chloroquine therapy. Clin. Sci. 44, 571–581 (1973)PubMedGoogle Scholar
  143. Timme, A.H., Taljaard, J.J.F., Shanley, B.C., Joubert, S.M.: Symptomatic porphyria. II. Hepatic changes with hexachlorobenzene. S. Afr. med. J. 48, 1833–1836 (1974)PubMedGoogle Scholar
  144. Tomio, J.M., Garcia, R.C., San Martin de Viale, L.C., Grinstein, M.: Porphyrin biosynthesis. VII. Porphyrinogen carboxy-lyase from avian erythrocytes. Purification and properties. Biochim. biophys. Acta (Amst.) 198, 353–363 (1970)PubMedGoogle Scholar
  145. Tschudy, D.P., Bonkowsky, H.L.: Experimental porphyria. Fed. Proc. 31, 147–159 (1972)PubMedGoogle Scholar
  146. Turnbull, A., Baker, H., Vernon-Roberts, B., Magnus, I.A.: Iron metabolism in porphyria cutanea tarda and erythropoietic protoporphyria. Quart. J. Med., New Series 42, 341–355 (1973)Google Scholar
  147. Turner, J.C., Green, R.S.: Effect of hexachlorobenzene on microsomal enzyme systems. Biochem. Pharmacol. 23, 2387–2390 (1974)PubMedGoogle Scholar
  148. Villeneuva, E.C., Jennings, R.W., Burse, V.M., Kimbrough, R.D.: Evidence of chlorodibenzo-p-dioxin and chlorodibenzofuran in hexachlorobenzene. J. agric. Food Chem. 22, 916–917 (1974)Google Scholar
  149. Villeneuve, D.C.: The effect of food restriction on the redistribution of hexachlorobenzene in the rat. Toxicol, app. Pharmacol. 31, 313–319 (1975)Google Scholar
  150. Villeneuve, D.C., Phillips, W.E.J., Panopio, L.G., Mendoza, C.E., Hatina, G.V., Grant, D.L.: The effects of phenobarbital and carbon tetrachloride on the rate of decline of body burdens of hexachlorobenzene in the rat. Arch. environ. Contam. Toxicol. 2, 243–252 (1974)PubMedGoogle Scholar
  151. Vinopal, J.N., Casida, J.E.: Metabolic stability of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mammalian liver microsomal systems and in living mice. Arch, environ. Contam. Toxicol. 1, 122–132 (1973)Google Scholar
  152. Vos, J.G., Beems, R.B.: Dermal toxicity studies of technical polychlorinated biphenyls and fractions there of in rabbits. Toxicol, appl. Pharmacol. 19, 617–633 (1971)Google Scholar
  153. Vos, J.G., Botterweg, P.F., Strik, J.J.T.W.A., Koeman, J.H.: Experimental studies with HCB in birds. TNO-nieuws 27, 599–603 (1972)Google Scholar
  154. Vos, J.G., Koeman, J.H.: Comparative toxicologic study with polychlorinated biphenyls in chickens with special reference to porphyria, edema formation, liver necrosis, and tissue residues. Toxicol, appl. Pharmacol. 17, 656–668 (1970)Google Scholar
  155. Vos, J.G., Koeman, J.H., Van der Maas, H.L., Ten Noever de Brauw, M.C., De Vos, R.H.: Identification and toxicological evaluation of chlorinated dibenzofurans and chlorinated naphthalene in two commercial polychlorinated biphenyls. Food Cosmet. Toxicol. 8, 625–633 (1970)PubMedGoogle Scholar
  156. Vos, J.G., Notenboom-Ram, E.: Comparative toxicity study of 2,4,5,2′,4′,5′-hexachlorobiphenyl and a polychlorinated biphenyl mixture in rabbits. Toxicol, appl. Pharmacol. 23, 563–578 (1972)Google Scholar
  157. Vos, J.G., Van der Maas, H.L., Musch, A., Ram, E.: Toxicity of hexachlorobenzene in Japanese Quail with special reference to porphyria, liver damage, reproduction and tissue residues. Toxicol, appl. Pharmacol. 18, 944–957 (1971)Google Scholar
  158. Wada, O., Yano, Y., Urata, G., Nakao, K.: Behaviour of hepatic microsomal cytochromes after treatment of mice with drugs known to disturb porphyrin metabolism in liver. Biochem. Pharmacol. 17, 595–603 (1968)PubMedGoogle Scholar
  159. Watson, C.J.: The problem of porphyria–some facts and questions. New Engl. J. Med. 263, 1205–1215 (1960)PubMedGoogle Scholar
  160. Wolf, M., Lester, R., Schmid, R.: Hepatic GSH in hexachlorobenzene induced porphyria. Biochem. biophys, Res. Commun. 8, 278–279 (1962)Google Scholar
  161. Woods, J.S.: Studies of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on mammalian hepatic δ-aminolaevulinic acid synthetase. Environ. Hlth. Perspect. 5, 221–225 (1973)Google Scholar
  162. Wray, J.D., Müftü, Y., Dogramaci, I.: Hexachlorobenzene as a cause of porphyria turcica. Turk. J. Pediat. 4, 132–137 (1962)Google Scholar

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© Springer-Verlag Berlin Heidelberg 1978

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  • G. H. Elder

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