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Retinoids as Chemopreventive Agents: Alone and in Combination

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Vitamins and Cancer

Part of the book series: Experimental Biology and Medicine, Vol. 10 ((EBAM,volume 10))

Abstract

The role of retinoids in cancer chemoprevention has been the subject of numerous studies. The rationale for the use of retinoids as chemopreventive agents or inhibitors of carcinogenesis dates back more than 60 years. As early as 1922, Mori (35) observed that a deficiency in vitamin A led to metaplastic changes of the epithelium of the respiratory tract; the normal ciliated columnar epithelium became flattened, lost nuclei, and became cornified while the underlying cells exhibited typical keratohyalin granules. Subsequent studies by Wolbach and Howe (47) extended these observations to epithelia of the gastrointestinal and urinary tracts. These observations of Mori and those of Wolbach and Howe on the development of such retinoid deficient squamous metaplasia indicated a process closely akin to that induced by certain chemical carcinogens (9). A more direct link between retinoids and cancer appeared in 1926 when Fujimaki (5) observed the development of carcinomas of the stomach in rats maintained on a vitamin A deficient diet. More recently, other investigators have shown that animals fed a diet deficient in retinoids and subsequently exposed to chemical carcinogens develop a greater than normal incidence of cancers and putative precursors to these malignancies (37).

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References

  1. Bashor, M.M., Toft, D.O., and Chytil, F. In vitro binding of retinol to rat tissue components. Proc. Natl. Acad. Sci.,70:3483–3487, 1973.

    Article  PubMed  CAS  Google Scholar 

  2. Becci, P.J., Thompson, H.J., Grubbs, C.J., Brown, C.C. and Moon, R.C. Effect of delay in administration of 13-cis-retinoic acid on the inhibition of urinary bladder carcinogenesis in the rat. Cancer Res., 39: 3141–3144, 1979.

    PubMed  CAS  Google Scholar 

  3. Chytil, F., and Ong, D.E. Cellular retinoid-binding proteins. In: Sporn, M.B., Roberts, A.B., and Goodman D.S. (eds.), The Retinoids, Vol. 2, Academic Press, Orlando, pp. 97–110.

    Google Scholar 

  4. Cohen, S.M., Wittenberg, J.F., and Bryan, G.T. Effect of avitaminosis A and hypervitaminos is A on urinary bladder carcinogenecity of N-[4-(5-nitro-2-furyl)-2- thiazolylformamide. Cancer Res., 36: 2334–2339, 1976.

    PubMed  CAS  Google Scholar 

  5. Fujimaki, Y. Formation of carcinoma in albino rats fed on deficient diets. J. Cancer Res., 10: 469–477, 1926.

    Google Scholar 

  6. Grubbs, C.J., Moon, R.C., Squire, R.A., Farrow, G.M., Stinson, S.F., Goodman, D.G., Brown, C.B., and Sporn, M.B. 13-cis-Retinoic acid: Inhibition of bladder carcinogenesis induced in rats by N-butyl-N- (4-hydroxybutyl)nitrosamine. Science, 198: 743–747, 1977.

    Article  PubMed  CAS  Google Scholar 

  7. Gullino, P.M., Pettigrew, H.M., and Grantham, F.H. N-nitrosomethylurea as mammary gland carcinogen in rats. J. Natl. Cancer Inst., 54: 401–414, 1975.

    PubMed  CAS  Google Scholar 

  8. Harisiadis, L., Miller, R.C., Hall, E.J., and Borek, C. A vitamin A analogue inhibits radiation-induced oncogenic transformation. Nature, 274: 486–487, 1978.

    Article  PubMed  CAS  Google Scholar 

  9. Harris, C.C., Sporn, M.B., Kaufman, D.G., Smith, J.M., Jackson, F.E., and Saffiotti, U. Histogenesis of squamous metaplasis in the hamster tracheal epithelium caused by vitamin A deficiency or benzo(α)pyrene- ferric oxide. J. Natl. Cancer Inst., 48: 743–761, 1972.

    PubMed  CAS  Google Scholar 

  10. Hultin, T.A., and Moon, R.C. Metabolism of N-(4- hydroxyphenyl)retinamide in female rats and mice. Fed. Proc., 44: 1338, 1985.

    Google Scholar 

  11. Ip, C., and Ip, M.M. Chemoprevention of mammary tumor- igenesis by a combined regimen of selenium and vitamin A. Carcinogenesis, 2: 915–918, 1981.

    Article  PubMed  CAS  Google Scholar 

  12. Lasnitzki, I., and Goodman, D.S. Inhibition of the effects of methylcholanthrene on mouse prostate in organ culture by vitamin A and its analogs. Cancer Res., 34: 1564–1571, 1974.

    PubMed  CAS  Google Scholar 

  13. Maiorana, A., and Gullino, P. Effect of retinyl acetate on the incidence of mammary carcinomas and hepatomas in mice. J. Natl. Cancer Inst., 64: 655–663, 1980.

    PubMed  CAS  Google Scholar 

  14. McCormick, D.L., Adamowski, C.B., Fiks, A., and Moon, R.C. Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl- N-nitrosourea. Cancer Res., 41: 1690–1694, 1981.

    PubMed  CAS  Google Scholar 

  15. McCormick, D.L., Becci, P.J., and Moon, R.C. Inhibition of mammary and urinary bladder carcinogenesis by a retinoid and a maleic anhydride-divinyl ether copolymer (MVE-2). Carcinogenesis, 3: 1473–1477, 1982.

    Article  PubMed  CAS  Google Scholar 

  16. McCormick, D.L., Burns, F.J., and Albert, R.E. Inhibition of benzo(α)pyrene-induced mammary carcinogenesis by retinyl acetate. J. Natl. Cancer Inst., 66: 559–564, 1981.

    PubMed  CAS  Google Scholar 

  17. McCormick, D.L., Mehta, R.G., Thompson, C.A., Dinger, N., Caldwell, J.A., and Moon, R.C. Enhanced inhibition of mammary carcinogenesis by combination N-(4- hydroxyphenyl)retinamide and ovariectomy. Cancer Res., 42: 509–512, 1982.

    Google Scholar 

  18. McCormick, D.L., and Moon, R.C. Influence of delayed administration of retinyl acetate on mammary carcinogenesis. Cancer Res., 42: 2639–2643, 1982.

    PubMed  CAS  Google Scholar 

  19. Mehta, R.G., Cerny, W.L., and Moon, R.C. Distribution of retinoic acid-binding protein in normal and neoplastic mammary tissues. Cancer Res., 40: 47–49, 1980.

    PubMed  CAS  Google Scholar 

  20. Mehta, R.G., Cerny, W.L., and Moon, R.C. Nuclear interaction of retinoic acid binding protein in chemically induced mammary adenocarcinomas. Biochem. J., 208: 731–736, 1982.

    PubMed  CAS  Google Scholar 

  21. Mehta, R.G., Cerny, W.L., and Moon, R.C. Alteration in DNA-dependent RNA polymerase activity by retinoids. Proc. Am. Ass. Cancer Res., 23: 21, 1982.

    Google Scholar 

  22. Mehta, R.G., Cerny, W.L., and Moon, R.C. Retinoid inhibition of prolactin-induced development of the mammary gland in vitro. Carcinogenesis (Lond.), 4: 23–26, 1983.

    Article  CAS  Google Scholar 

  23. Mehta, G.R., Kute, T.E., Hopkins, M., and Moon, R.C. Retinoic acid-binding proteins and steroid receptor levels in human breast cancer. Eur. J. Cancer Clin. Oncol., 18: 221–226, 1982.

    Article  PubMed  CAS  Google Scholar 

  24. Mehta, R.G., McCormick, D.L., Cerny, W.L., and Moon, R.C. Correlation between retinoid inhibition of N- methyl-N-nitrosourea-induced mammary carcinogenesis and levels of retinoic acid-binding proteins. Carcinogenesis, 3: 89–91, 1982.

    Article  PubMed  CAS  Google Scholar 

  25. Mehta, R.G., and Moon, R.C. Hormonal regulation of retinoic acid-binding proteins in the mammary gland. Biochem. J., 200: 591–595, 1981.

    PubMed  CAS  Google Scholar 

  26. Mehta, R.G., and Moon, R.C. Inhibition of DNA synthesis by retinyl acetate during chemical1y-induced mammary carcinogenesis. Cancer Res., 40: 1109–1111, 1981.

    Google Scholar 

  27. Merriman, R.L., and Bertram, J.S. Reversible inhibition by retinoids of 3-methyl-cholanthrene-induced neoplastic transformation in C3H/10T1/2 CL8 cells. Cancer Res., 39: 1661–1666, 1979.

    PubMed  CAS  Google Scholar 

  28. Moon, R.C. Influence of pregnancy and lactation on experimental mammary carcinogenesis. In: Pike, M.C., Siiteri, P.K., and Welsch, C.W. (eds.), Hormones and Breast Cancer, Banbury Report 8, Cold Spring Harbor Laboratory, 1981.

    Google Scholar 

  29. Moon, R.C., and Mehta, R.G. Retinoid binding in normal and neoplastic mammary tissue. In: W.W. Leavit (ed.), Hormones and Cancer, pp. 231–249 New York: Plenum Publishing Corp., 1982.

    Google Scholar 

  30. Moon, R.C., McCormick, D.L., and Mehta, R.G. Inhibition of carcinogenesis by retinoids. Cancer Res., 43, 2469s–2475s, 1983.

    PubMed  CAS  Google Scholar 

  31. Moon, R.C., Grubbs, C.J., and Sporn, M.B. Inhibition of 7,12-dimethyl-benz(α)anthracene-induced mammary carcinogenesis by retinyl acetate. Cancer Res., 36: 2626–2630, 1976.

    PubMed  CAS  Google Scholar 

  32. Moon, R.C., Grubbs, C.J., Sporn, M.B., and Goodman, D.G. Retinyl acetate inhibits mammary carcinogenesis induced by N-methyl-N-nitrosourea. Nature, 267: 620–621, 1977.

    Article  PubMed  CAS  Google Scholar 

  33. Moon, R.C., Mehta, R.G., and McCormick, D.L. Modulation of mammary carcinogenesis by retinoids. In: K.N. Prasad (ed.), Vitamins, Nutrition and Cancer, pp. 20–32, Basel, Karger, 1984.

    Google Scholar 

  34. Moon, R.C., Thompson, H.J., Becci, P.J., Grubbs, C.J., Gander, R.J., Newton, D.L., Smith, J.M., Phillips, S.R., Henderson, W.R., Mullen, L.T., Brown, C.C., and Sporn, M.B. N-(4-hydroxypheny1)retinamide, a new retinoid for prevention of breast cancer in the rat. Cancer Res., 39: 1339–1346, 1979.

    PubMed  CAS  Google Scholar 

  35. Mori, S. The changes in the para-ocular glands which follow the administration of diets low in fat-soluable A; with notes of the effects of the same diets on the salivary glands and the mucosa of the larynx and trachea. Johns Hopkins Hosp. Bull., 33, 357–359, 1922.

    CAS  Google Scholar 

  36. Smith, F.R., and Goodman, D.S. Vitamin A transport and human vitamin A toxicity. New Engl. J. Med., 294: 805–808, 1976.

    Article  PubMed  CAS  Google Scholar 

  37. Sporn, M.B., Dunlop, N.M., Newton, D.L., and Smith, J.M. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed. Proc., 35: 1332–1338, 1976.

    PubMed  CAS  Google Scholar 

  38. Sporn, M.B., Squire, R.A., Brown, C.C., Smith, J.M., Wenk, M.L., and Springer, S. 13-cis-Retinoic acid: Inhibition of bladder carcinogenesis in the rat. Science, 195: 487–489, 1977.

    Article  PubMed  CAS  Google Scholar 

  39. Thompson, H.J., Meeker, L.D., and Becci, P.J. Effect of combined selenium and retinyl acetate treatment on mammary carcinogenesis. Cancer Res., 41: 1413–1416, 1981.

    PubMed  CAS  Google Scholar 

  40. Todaro, G.J., DeLarco, J.E., and Sporn, M.B. Retinoids block phenotypic cell transformation produced by sarcoma growth factor. Nature, 276: 272, 1978.

    Article  PubMed  CAS  Google Scholar 

  41. Verma, A.K., and Boutwell, R.K. Vitamin A acid (retinoic acid), a potent inhibitor of 12-0-tetradec- anoyl-phorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis. Cancer Res., 37: 2196–2201, 1977.

    PubMed  CAS  Google Scholar 

  42. Verma, A.K., Shapas, B.G., Rice, H.M., and Boutwell, R.K. Correlation of the inhibition by retinoids of tumor promoter-induced mouse epidermal ornithine decarboxylase activity and of skin tumor promotion. Cancer Res., 39: 419–425, 1979.

    PubMed  CAS  Google Scholar 

  43. Welsch, C.W., Brown, C.K., Goodrich-Smith, M., Chuisano, J., and Moon, R.C. Synergistic effect of chronic prolactin suppression and retinoid treatment in the prophylaxis of N-methyl-N-nitrosourea-induced mammary tumorigenesis in female Sprague-Dawley rats. Cancer Res., 40: 3095–3098, 1980.

    PubMed  CAS  Google Scholar 

  44. Welsch, C.W., and Doog, J.V. Retinoid feeding, hormone inhibition and/or immune stimulation and the genesis of carcinogen-induced rat mammary carcinomas. Cancer Res., 43: 585–591, 1983.

    PubMed  CAS  Google Scholar 

  45. Welsch, C.W., Goodrich-Smith, M., Brown, C.K., and Crowe, N. Enhancement by retinyl acetate of hormone- induced mammary tumorigenesis in female GR/A mice. J. Natl. Cancer Inst., 67: 935–938, 1981.

    PubMed  CAS  Google Scholar 

  46. Welsch, C.W., Goodrich-Smith, M., Brown, C.K., Mackie, D., and Johnson, D. 2-Bromo-α-ergocryptine (CB 154 and tamoxifen C1C1 46474) induced suppression of the genesis of mammary carcinoma in female rats treated with 7–12-dimethylbenz(α)anthracene (DMBA): a comparison. Oncology, 39: 88–92, 1982.

    Article  PubMed  CAS  Google Scholar 

  47. Wolbach, S.D., and Howe, P.R. Tissue changes following deprivation of fat-soluble A vitamin. J. Exp. Med., 42: 753–777, 1925.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. IIT Research Institute, 10 West 35th Street, 60617, Chicago, IL, USA

    R. C. Moon, D. L. McCormick & R. G. Mehta

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  1. R. C. Moon
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  2. D. L. McCormick
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  3. R. G. Mehta
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Editors and Affiliations

  1. Section of Hematology/Oncology, Cancer Center, Arizona Health Sciences Center, Tucson, AZ, USA

    Frank L. Meyskens Jr.

  2. Center of Vitamins and Cancer Research Department of Radiology, University of Colorado Health Sciences Center, Denver, CO, USA

    Kedar N. Prasad

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© 1986 The Humana Press Inc.

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Moon, R.C., McCormick, D.L., Mehta, R.G. (1986). Retinoids as Chemopreventive Agents: Alone and in Combination. In: Meyskens, F.L., Prasad, K.N. (eds) Vitamins and Cancer. Experimental Biology and Medicine, Vol. 10, vol 10. Humana Press. https://doi.org/10.1007/978-1-4612-5006-7_10

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  • DOI: https://doi.org/10.1007/978-1-4612-5006-7_10

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-9395-8

  • Online ISBN: 978-1-4612-5006-7

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