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Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of dibenzo[a]pyrenes: the very potent environmental carcinogen dibenzo[a, l]pyrene

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Summary

Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with several dibenzo[a]-pyrenes (DBPs). SENCAR mice were initiated with DB[a,e]P, DB[a,h]P, DB[a,i]P, DB[a,l]P and anthanthrene, and promoted with tetradecanoyl-phorbol acetate. The same compounds were tested by intramammillary injection in female Sprague-Dawley rats. Anthanthrene was inactive in both mouse skin and rat mammary gland. DB[a,e]P was a very weak tumor-initiator in mouse skin and was inactive in rat mammary gland. DB[a,h]P induced twice as many papillomas in mouse skin as DB[a,i]P, although both compounds exhibited similar tumor latencies and percentages of tumor-bearing mice. These two compounds induced similar numbers of mammary tumors, but treatment of the rats with DB[a,i]P resulted in a significantly larger number of adenocarcinomas. DB[a,l]P was toxic to both the mice and rats. Treatment of mouse skin with this compound led to an erythema, which delayed the beginning of promotion until the 3rd week after initiation. Despite this delay, papillomas began appearing 5 weeks after initiation with DB[a,l]P and the number of tumors increased rapidly. The compound was so toxic in the rats that half of the animals died in the first 9 weeks and the remaining animals were sacrificed after 15 weeks. Nonetheless, DB[a,l]P was the strongest carcinogen tested, inducing seven tumors per rat within 10 weeks. These results demonstrate that DB[a,l]P, which is present in tobacco smoke, is an extremely potent carcinogenic aromatic hydrocarbon. Furthermore, some of these compounds can serve as useful models for elucidating their mechanisms of activation.

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Abbreviations

DBP:

dibenzo[a]pyrene

References

  1. Carruthers W (1966) Synthesis of dilbenzo[a,l]pyrene. Chem Commun. 548–549

  2. Cavalieri E, Rogan E (1985a) One-electron oxidation in aromatic hydrocarbon carcinogenesis. In: Harvey RG (ed) ACS Symposium Series no. 283, Polycyclic hydrocarbons and carcinogenesis. American Chemical Society. Washington, D.C., pp 289–305

  3. Cavalieri E, Rogan E (1985b) Metabolic activation by one-electron and two-electron oxidation in aromatic hydrocarbon carcinogenesis. In: Woo Y-T, Lai DY, Arcos JC, Argus MF (eds) Chemical induction of cancer, vol IIIB. Academic Press, New York, pp 533–569

  4. Cavalieri E, Rogan E (1985c) Role of radical cations in aromatic hydrocarbon carcinogenesis. Environmental Health Perspectives 64:69–84

  5. Cavalieri E, Mailander P, Pelfrene A (1977) Carcinogenic activity of anthanthrene on mouse skin. Z Krebsforsch 89:113–118

  6. Cavalieri E, Rogan E, Higginbotham S, Cremonesi P (1986) Carcinogenicity in mouse skin and rat mammary gland of benzo[a]-pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) derivatives refuting the diol-epoxide theory. Proc Amer Assoc Cancer Res 27:93

  7. Chang RL, Levin W, Wood AW, Lehr RE, Kumar S, Yagi H, Jerina DM, Conney AH (1982) Tumorigenicity of bay-region diol-epoxides and other benzo-ring derivatives of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene on mouse skin and in newborn mice. Cancer Res 42:25–29

  8. Conney AH (1982) Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G.H.A. Clowes Memorial Lecture. Cancer Res 42:4875–4917

  9. Deutsch-Wenzel RP, Brune H, Grimmer G, Dettbarn G, Misfeld J (1983) Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurrring environmental polycyclic aromatic hydrocarbons. J Natl Cancer Inst 71:539–544

  10. Hoffmann D, Wynder EL (1966) Beitrag zur carcinogenen Wirkung von Dibenzopyrenen. Z Krebsforsch 68:137–149

  11. IARC (1973) IARC monographs on the evaluation of carcinogenic risk of the chemical to man, vol 3, Certain polycyclic aromatic hydrocarbons and heterocyclic compounds. IARC, Lyon, (a) pp 201–228; (b) pp 207–223

  12. IARC (1983) IARC monographs on the evaluation of carcinogenic risk of chemicals to humans, vol 32, Polynuclear aromatic compounds, part 1. Chemical, environmental and experimental data. IARC, Lyon, (a) pp 33–104, 327–347; (b) pp 33–53; (c) pp 343–347

  13. Karcher W, Fordham RJ, Dubois JJ, Glaude PGJM, Lightart JAM (1985) Spectral atlas of polycyclic aromatic compounds. D Reidel Publishers, Boston, pp 760–761

  14. Konieczny M, Harvey RG (1979) Efficient reduction of polycyclic quinones, hydroquinones, and phenols to polycyclic aromatic hydrocarbons with hydriodic acid. J Org Chem 44:4813–4816

  15. Lacassagne A, Buu-Hoï NP, Zajdela F (1958) Relation entre structure moleculaire et activité cancérogène dans trois series d'hydrocarbures aromatiques hexacycliques. CR Acad Sci 246:1477–1480

  16. Lacassagne A, Buu-Hoï NP, Zajdela F, Lavit-Lamy D (1963) Activité cancérogène elevée du 1,2,3,4-dibenzopyrène et 1,2,4,5-dibenzopyrène. CR Acad Sci 256:2728–2730

  17. Lacassagne A, Buu-Hoï NP, Zajdela F, Vingiello FA (1968) The true dibenzo[a,l]pyrene, a new potent carcinogen. Naturwissenschaften 55:43

  18. Lavit-Lamy D, Buu-Hoï NP (1966) The true nature of “dibenzo[a,l]-pyren” and its known derivatives. Chem Commun 92–94

  19. Lee ML, Novotny M (1976) Gas chromatography/mass spectrometric and nuclear magnetic resonance determination of polynuclear aromatic hydrocarbons in airborne particulates. Anal Chem 48:1566–1572

  20. Lijinsky W, Garcia H (1972) Skin carcinogenesis tests of hydrogenated derivatives of anthanthrene and other polynuclear hydrocarbons. Z Krebsforsch 77:226–230

  21. Masuda Y, Kagawa R (1972) A novel synthesis and carcinogenicity of dibenzo[a,l]pyrene. Chem Pharm Bull (Tokyo) 20:2736–2737

  22. Scribner JD (1973) Brief communication: tumor initiation by apparently noncarcinogenic polycyclic aromatic hydrocarbons. J Natl Cancer Inst 50:1717–1719

  23. Sims P, Grover PL (1981) Involvement of dihydrodiols and diol epoxides in the metabolic activation of polycyclic hydrocarbons other than benzo[a]pyrene. In: Gelboin HV, Ts'o POP (eds) Polycyclic hydrocarbons and cancer, vol 3. Academic Press, New York, pp 117–181

  24. Snook ME, Severson RF, Arrendale RF, Higman HC, Chortyk OT (1977) The identification of high molecular weight polynuclear aromatic hydrocarbons in a biologically active fraction of cigarette smoke condensate. Beitr Tabakforsch 9:79–101

  25. Van Duuren BL, Sivak A, Langseth L, Goldschmidt BM, Segal A (1986) Inrtiators and promotors in tobacco carcinogenesis. Natl Cancer Inst Monogr 28:173–180

  26. Vingiello FA, Yanez J, Greenwood EJ (1966) The synthesis of dibenzo[a,l]pyrene. Chem Commun 375–377

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Author information

Correspondence to Ercole L. Cavalieri.

Additional information

This research was supported by Public Health Service grants CA32376 and CA25176 from the National Cancer Institute and by institutional grants CA36727 from the National Cancer Institute and ACS SIG-16 from the American Cancer Society

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Cavalieri, E.L., Rogan, E.G., Higginbotham, S. et al. Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of dibenzo[a]pyrenes: the very potent environmental carcinogen dibenzo[a, l]pyrene. J Cancer Res Clin Oncol 115, 67–72 (1989). https://doi.org/10.1007/BF00391602

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Key words

  • Mouse skin
  • Rat mammary gland
  • Tumorigenicity
  • Dibenzo[a]pyrenes