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Cocarcinogenic and tumor-promoting capabilities of anthralin

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Summary

Numerous chemicals to which humans are exposed either therapeutically or as a result of living in an industrial environment constitute a potential threat as carcinogens, mutagens, and/or tumor promoters and cocarcinogens. Anthralin, and antipsoriatic agent, acts as a tumor promoter for Balb/c-3T3 mouse embryo cell cultures that were previously exposed to a low dose of either benzo-a-pyrene (BaP), an indirect-acting carcinogen needing metabolic conversion for its carcinogenic action, or β-propiolactone (BPL), a direct-acting carcinogen which needs no metabolic conversion. As a cocarcinogen, i.e., when exposure of cells to anthralin was simultaneous with exposure to the carcinogen, anthralin enhanced neoplastic transformation only when the carcinogen was BaP. Several explanations are explored. The possibility that cocarcinogens and tumor promotion occur by separate mechanisms is suggested.

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References

  1. Ashton AE, Andre P, Lowe NJ, Whitefield M (1983) Anthralin: Historical and current perspectives. J Am Acad Dermatol 9:173–192

    Google Scholar 

  2. Atchison M, Chu C, Kakunaga T, Van Duuren BL (1982) Chemical cocarcinogenesis with the use of subclone derived from BALB/3T3 cells with catechol as a cocarcinogen. NCI 69:503–508

    Google Scholar 

  3. Baird WM, Salmon CP, Diamond L (1984) Benzo(a)pyrene induced alterations in the metabolic activation of benzo(a)pyrene and 7,12-dimethylbenz(a)anthrecene by hamster embryo cells. Cancer Res 44:1445–1452

    Google Scholar 

  4. Barrett JC, Ts'o POP (1978) Evidence for the progressive nature of neoplastic transformation in vitro. Proc Natl Acad Sci (USA) 75:3761–3765

    Google Scholar 

  5. Baturay NZ, Kennedy AR (1986) Pyrene acts as a cocarcinogen with the carcinogens benzo(a)pyrene, B-propiolactone and radiation in the induction of malignant transformation in cultured mouse fibroblasts; soybean extract containing the Bowman-Birk inhibitor acts as an anticarcinogen. Cell Biol Toxicol 2:21–32

    Google Scholar 

  6. Berenblum I (1975) Sequential aspects of chemical cocarcinogenesis: skin. In: Becker F (ed) Cancer, a comprehensive treatise, vol 1. Plenum Press, New York, pp 323–339

    Google Scholar 

  7. Berwald Y, Sachs L (1965) In vitro transformation of normal cells to tumor cells by carcinogenic hydrocarbons. JNCI 35:641–661

    Google Scholar 

  8. Bock G, Burns R (1963) Tumor promoting properties of anthralin (1,8,9-anthratriol). JNCI 30:393–398

    Google Scholar 

  9. Boutwell RK (1978) Biochemical mechanisms of tumor promotion. In: Slaga TJ, Sivak A, Boutwell RN (eds) Carcinogenesis, vol 2, Mechanisms of tumor promotion and cocarcinogenesis. Raven Press, New York, pp 49–58

    Google Scholar 

  10. Boutwell RK, Hoel MJ, Digiovanni J (1981) The role of anthralin in mouse skin tumor promotion. Br J Dermatol 105 [Suppl 20]:68–69

    Google Scholar 

  11. Clark JM, Hanawalt PC (1982) Inhibition of DNA replication and repair by anthralin or Danthron in cultured human cells. J Invest Dermatol 79:18–22

    Google Scholar 

  12. Cortesi E, Saffiotti U, Donovan PJ, Rice JM, Kakunaga T (1983) Dose response studies on neoplastic transformation of BalB 3T3 clone A-31-1-1 cells by aflatoxin B1 benzidine, benzo(a)pyrene, 3-methylcholanthrene and N-nitrosamine. Teratogenesis Carcinog Mutagen 3:101–110

    Google Scholar 

  13. Doll R, Peto R (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. JNCI 66:1191–1308

    Google Scholar 

  14. Finnen MJ, Lawrence CM, Shuster S (1984) Inhibition of dithranol inflammation by free-radical scavengers. Lancet 2:1129–1130

    Google Scholar 

  15. Gorsulowsky DC, Voorhees JJ, Ellis CN (1985) Anthralin therapy for psoriasis. A new look at an old compound. Arch Dermatol 121:1509–1511

    Google Scholar 

  16. Hecker E (1968) Cocarcinogenic principles from the seed oil of Croton tiglium and other euphorbiaceae. Cancer Res 28:2338

    Google Scholar 

  17. Kakunaga T (1973) A quantitative system for assay of malignant transformation by chemical carcinogens using a colone derived from BALB/3T3. Int J Cancer 12:463–473

    Google Scholar 

  18. Kakunaga T (1985) Critical review of the use of established cell lines for in vitro cell transformation. In: Kakunga T, Yamasaki H (eds) Transformation assay of estalished cell lines: mechanisms and application. IARC Scientific Publications 67, pp 55–73

  19. Kennedy AR (1984) Promotion and other interactions between agents in the induction of transformation in vitro in fibroblasts. In: Slaga TJ (ed) Mechanics of tumor promotion, vol 3. Tumor promotion and carcinogenesis in vitro. CRC Press, Baca Raton, Fl. pp 13–55

    Google Scholar 

  20. Kennedy AR, Little JB (1980) Radiation tranformation in vitro: modification by exposure to tumor promotors and protease inhibitors. In: Meyn RE, Withers HR (eds) Radiation biology in cancer research. Raven Press, New York, pp 295–307

    Google Scholar 

  21. Kennedy AR, Murphy G, Little JB (1980) Effect of time and duration of exposure to TPA on X-ray transformation of C3H 10T 1/2 cells. Cancer Res 40:1915–1920

    Google Scholar 

  22. Little JB (1979) Quantitative studies of radiation transformation with the A31-11 mouse BALB/3T3 cell line. Cancer Res 39:1474–1480

    Google Scholar 

  23. MacPherson I (1973) Soft agar techniques. In: Kruse PF, Patterson MK (eds) Tissue culture, methods and applications. Academic Press, New York, pp 276–280

    Google Scholar 

  24. Martinmaa J, Juselius J, Mustakallio KK (1981) Free radicals by autoxidation of dithranol (anthralin) and its analogs. In: Farber EM, Cox AJ (eds) Proceedings of the Third International Symposium of Psoriasis. Grune and Stratton, New York, pp 383–384

    Google Scholar 

  25. McNeill JM, Gower J-D, Wills ED (1985) The formation of the ultimate carcinogen of benzo(a)pyrene during non-enzymic lipid peroxidation. Biochem Pharmol 34:4068–4071

    Google Scholar 

  26. Melikian AA, Leszczynska JM, Hect SS, Hoffmann D (1986) Effects of the co-carcinogen catechol on benzo(a)pyrene metabolism and DNA adduct formation in mouse skin. Carcinogenesis 7:9–15

    Google Scholar 

  27. Mondal S, Heidelberger C (1976) Transformation of C3H/10T 1/2 C18 mouse embryo fibroblasts by ultraviolet irradiation and a phorbol ester. Nature 260:710–711

    Google Scholar 

  28. Mustakallio KK (1981) Irritation, staining and antipsoriatic activity of 10-acyl analogues of anthralin. Br J Dermatol 105 [Suppl 20]:23–27

    Google Scholar 

  29. Pelkonen O, and Nebert DW (1982) Metabolism of polycyclic aromatic hydrocarbons: etiologic role in carcinogenesis. Pharmacol Rev 34:189–221

    Google Scholar 

  30. Segal A, Katz C, Van Duuren BL (1971) Structure and tumor promoting activity of anthralin (1,8-dihydroxy-9-anthrone) and related compounds. J Med Chem 14:1152–1154

    Google Scholar 

  31. Selkrik JK, Merrick BA, Schaeffer EL, Mann RC, Mansfield BK (1986) The role of metabolism in benzo(a)pyrene carcinogenesis. In: Claes Ramel et al. (eds) Genetic toxicology of environmental chemicals, part A: Basic principles and mechanisms of action. Alan R. Liss, New York, pp 483–493

    Google Scholar 

  32. Sims P, Grover PL, Swaisland A, Pal K, Hewer A (1974) Metabolic activation of benzo(a)pyrene proceeds by a diolepoxide. Nature 25:326–328

    Google Scholar 

  33. Smolarek TA, Moynihan CG, Salmon CP, Baird WM (1986) Benz(a)anthracene induced alterations in the metabolic activation of benzo(a)pyrene by hamster embryo cell cultures. Cancer Lett 30:243–249

    Google Scholar 

  34. Swanbeck G, Liden S (1966) The inhibitory effect of dithranol (anthralin) on DNA synthesis. Acta Derm Venereol (Stockh) 46:228–230

    Google Scholar 

  35. Van Duuren BL, Goldschmidt BM (1976) Cocarcinogenic and tumor promoting agents in tobacco carcinogenesis. JNCI 56:1237–1242

    Google Scholar 

  36. Van Duuren BL, Segel A, Tseng SS, Tseng SS, Rusch GM, Loewengart F, Mate U, Roth D, Smith A, Melchionne S (1978) Structure and tumor-promoting activity of analogues and anthralin (1,8-dihydroxy-9-anthrone). J Med Chem 21:26–31

    Google Scholar 

  37. Yavelow J, Caggana M, Beck KA (1987) Proteases occurring in the cell membrane — a possible receptor for the Bowman-Birk type of protease inhibitor. Cancer Res 47:1598–1601

    Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy, St. John's University, 11439, Jamaica, NY, USA

    N. Z. Baturay & L. D. Trombetta

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  1. N. Z. Baturay
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  2. L. D. Trombetta
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Baturay, N.Z., Trombetta, L.D. Cocarcinogenic and tumor-promoting capabilities of anthralin. Arch Dermatol Res 280, 443–450 (1988). https://doi.org/10.1007/BF00429985

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  • DOI: https://doi.org/10.1007/BF00429985

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