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Pyrene acts as a cocarcinogen with the carcinogens benzo [a] pyrene, β-propiolactone and radiation in the induction of malignant transformation in cultured mouse fibroblasts; soybean extract containing the Bowman-Birk inhibitor acts as an anticarcinogen

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Abstract

Pyrene was found to act as a cocarcinogen in the induction of transformation of cultured Balb/c3T3 cells by three different types of carcinogens: a direct acting chemical carcinogen, β-propiolactone, a chemical carcinogen requiring metabolic activation, benzo[a]pyrene, and a physical carcinogen (60Co) gamma radiation. Since pyrene enhanced transformation in vitro by approximately the same amount for all the carcinogens tested, these results suggest that the carcinogenic action of pyrene is not related to carcinogen metabolism or uptake in vitro. An extract of soybeans containing the Bowman-Birk protease inhibitor was shown to reduce transformation induced by β-propiolactone, benzo[a]pyrene and γ-rays, both with and without the cocarcinogenic effect of pyrene, to background levels; the magnitude of the reduction in transformation by the protease inhibitor preparation was unrelated to the concentration of carcinogen. Neither the mechanism for the cocarcinogenic action of pyrene nor the anticarcinogenic effect of the soybean extract is known, but several hypotheses are discussed.

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Abbreviations

BaP:

benzo[a]pyrene

BBI:

Bowman-Birk inhibitor

BPL:

β-propiolactone

References

  • ATCHESON, M., CHU C., KAKUNAGA, T. and VAN DUUREN, B.L. (1982). Chemical cocarcinogenesis with the use of a subclone derived from Balb/3T3 cells with catechol as cocarcinogen. J. Natl. Cancer Inst. 69:503–508.

    Google Scholar 

  • BATURAY, N.Z., TARGOVNIK, H.S., REYNOLDS, R.J. and KENNEDY, A.R. (1985). Induction of in vitro transformation by near UV light and its interaction with Betapropiolactone. Carcinogenesis 6:465–468.

    Google Scholar 

  • BECKER, F.F. (1981). Inhibition of spontaneous hepatocarcinogenesis in C3H/HeN mice by Edi Pro A, an isolated soy protein. Carcinogenesis 2:1213–1214.

    Google Scholar 

  • BERENBLUM, I. (1975). Sequential aspects of chemical carcinogenesis: Skin. In: Cancer, A Comprehensive Treatise, Vol. I, F. Becker ed. Plenum Press, New York, pp. 323–339.

    Google Scholar 

  • CHEN, F.U. (1983). Binding of pyrene to DNA, base sequence specificity and its implication. Nucleic Acids Research 11:7231–7250.

    Google Scholar 

  • COPELAND, E.S. (1983). Free radicals in promotion-a chemical pathology study section workshop. Cancer Res. 43:5631–5637.

    Google Scholar 

  • CORTESE, E., SAFFIOTTI, U., DONOVAN, P.J., RICE, J.M. and KAKUNAGA, T. (1983). Dose-response studies on neoplastic transformation of Balb/3T3 clone A31–11 cells,by Aflatoxin B, Benzidine, BaP, 3-Methylcholanthrene and N-methyl-N1-nitro-N-nitroso-guanidine. Teratogenesis, Carcinogenesis, Mutagenesis 3:101–110.

    Google Scholar 

  • DOLL, R. and PETO, R. (1981). The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66:1191–1308.

    Google Scholar 

  • FREEDMAN, V.H. and SHIN, S. (1974). Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell 3:355–360.

    Google Scholar 

  • GOLDSTEIN, B.D., WITZ, G., AMORUSO, M. and TROLL, W. (1979). Protease inhibitors antagonize the activation of polymorphonuclear leukocyte oxygen consumption. Biochem. and Biophysical Res. Commun. 88:854–860.

    Google Scholar 

  • HEIDELBERGER, C. (1975). Chemical carcinogenesis. Ann. Rev. Biochem. 44:79–121.

    Google Scholar 

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

    Google Scholar 

  • KENNEDY, A.R. (1985, in press). Role of free radicals in the initiation and promotion of radiation-induced and chemical carcinogen induced cell transformation. In: Oxygen and Sulfur Radicals in Chemistry and Medicine, Proceedings of a Symposium held in Fermo, Italy, August 28–September 5, 1984.

  • KENNEDY, A.R. (1984). Promotion and other interactions between agents in the induction of transformation in vitro in fibroblasts. In: Mechanisms of Tumor Promotion, Vol. III. Tumor Promotion and Carcinogenesis in vitro, Slaga, T.J. ed. CRC Press, pp. 13–55.

  • KENNEDY, A.R., RADNER, B.S. and NAGASAWA, H. (1984). Protease inhibitors reduce the frequency of spontaneous chromosome abnormalities in cells from patients with Bloom syndrome. Proc. Natl. Acad. Sci. USA 81:1827–1830.

    Google Scholar 

  • KITAGAWA, S., TAKAKU, F. and SAKAMOTO, S. (1980). Evidence that proteases are involved in superoxide production by human polymorphonuclear leukocytes and monocytes. J. Clin. Invest. 65:74–81.

    Google Scholar 

  • LITTLE, J.B. (1979). Quantitative studies of radiation transformation with the A31–11 mouse BALB/3T3 cell line. Cancer Res. 39:1474–1480.

    Google Scholar 

  • LITTLE, J.B. and WILLIAMS, J.R. (1977). Effects of ionizing radiation on mammalian cells. In: Handbook of Physiology. Geiger, S.R., Falk, H.L., Murphy, S.D. and Lee, D.H.K., eds. American Physiological Society, Bethesda, MD, pp. 127–155.

    Google Scholar 

  • MACPHERSON, I. (1973). Soft agar techniques. In: Tissue Culture Methods and Applications. Kruse, P.F. and Patterson, M.K., eds. Academic Press, New York, pp. 276–280.

    Google Scholar 

  • MAHER, V.M., CURREN, R.D., OUELLETTE, L.M. and MCCORMICK, J.J. (1976). Effects of DNA repair on the frequency of mutations induced in human cells by UV irradiation and by chemical carcinogens. In: Fundamentals of Cancer Prevention. Magee, P.N., Takayama, S., Sugimura, T., Matsushima, T., eds. University of Tokyo Press, Tokyo, University Park Press, Baltimore, MD, pp. 363–82.

    Google Scholar 

  • MESSADI, P.V., BILLINGS, P., SHKLAR, G. and KENNEDY, A.R. (1985, in press). Inhibition of oral carcinogenesis by a protease inhibitor. J. Natl. Cancer Inst.

  • MEYN, M.S., ROSSMAN, T. and TROLL, W. (1977). A protease inhibitor blocks SOS functions in Escherichia coli; antipan prevents repressor inactivation, ultraviolet mutagenesis and filamentous growth. Proc. Natl. Acad. Sci. USA 74:1152–1156.

    Google Scholar 

  • SAFFIOTTI, U., RICE, J.M. and DONOVAN, P.J. (1979). Interactions of multiple carcinogens at low levels of exposure: Preliminary mutagenicity studies using Ames Salmonella system. In: Short-Term Tests for Prescreening Potential Carcinogens. L. Santi and S. Parodi, eds. Genova, Istituto Scientifico per lo Studio e la Cura dei Tumooi, pp. 98–109.

    Google Scholar 

  • SHAMBURGER, R.J. (1972). Increase in peroxidation in carcinogenesis. J. Natl. Cancer Inst., 48:1491–1497.

    Google Scholar 

  • SLAGA, T.J., KLEIN-SZANTO, A.J.P., TRIPLETT, L.L., YOTTI, L.P. and TROSKO, J.E. (1981). Skin tumor promoting activity of benzoyl peroxide, a widely used free radical generating compound. Science 21:1023–1025.

    Google Scholar 

  • TROLL, W., BELLMAN, S., WIESNER, R. and SHELLABARGER, C.J. (1979). Protease action in carcinogenesis. In: Biological Function of Proteinases. Holzer, H. and Tschesche, H., eds. Berlin, Springer-Verlag, pp. 165–170.

    Google Scholar 

  • TROLL, W.., MEYN, M.S. and ROSSMAN, T. (1977). Mechanisms of protease action in carcinogenesis. In: Carcinogenesis, Vol. II, Mechanisms of Tumor Promotion and Cocarcinogenesis. Slaga, T.J., Sivak, A. and Boutwell, R.K., eds. New York, Raven Press, pp. 301–312.

    Google Scholar 

  • VAN DUUREN, B.L. and GOLDSCHMIDT, B.M. (1976). Cocarcinogenic and tumor promoting agents in tobacco carcinogenesis. J. Natl. Cancer Inst. 56:1237–1242.

    Google Scholar 

  • VAN DUUREN, B.L., WITZ, G. and GOLDSCHMIDT, B. (1977). Structure-activity relationships of tumor promoters and cocarcinogens and interaction of phorbol myristate acetate and related esters with plasma membranes. In: Carcinogenesis: A Comprehensive Survey: Mechanisms of Tumor Promotion and Cocarcinogenesis. Slaga, T.J., Sivak, A. and Boutwell, R.K., eds. New York, Raven Press, pp. 491–507.

    Google Scholar 

  • WEED, H., MCGANDY, R.B. and KENNEDY, A.R. (1985). Protection against dimethylhydrazine induced adenomatous tumors of the mouse colon by the dietary addition of an extract of soybeans containing the Bowman-Birk protease inhibitor. Carcinogenesis 6:1239–1241.

    Google Scholar 

  • WEINSTEIN, I.B. (1980). Evaluating substances for promotion, cofactor effects and synergy in the carcinogenic process. J. Environ. Pathol. Toxicol. 3:89–101.

    Google Scholar 

  • WILLIAMS, G.M. (1984). Modulation of chemical carcinogenesis by xenobiotics. Fund. and Applied Tox. 4:325–344.

    Google Scholar 

  • YAVELOW, J., COLLINS, M., BIRK, Y., TROLL, W. and KENNEDY, A.R. (1985). Nanomolar concentrations of Bowman-Birk soybean protease inhibitor suppress x-ray induced transformation in vitro. Proc. Natl. Acad. Sci. USA 82:5395–5399.

    Google Scholar 

  • YAVELOW, J., FINLAY, T.H., KENNEDY, A.R. and TROLL, W. (1983). Bowman-Birk soybean protease inhibitor as an anticarcinogen. Cancer Res. (Suppl.) 43:2454–2459.

    Google Scholar 

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Baturay, N., Kennedy, A.R. Pyrene acts as a cocarcinogen with the carcinogens benzo [a] pyrene, β-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 (1986). https://doi.org/10.1007/BF00117704

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