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Antioxidants vs Carotenoids: Inhibitors or Promoters of Experimental Colorectal Cancers

Antioxidants vs Carotenoids: Inhibitors or Promoters of Experimental Colorectal Cancers Abstract • The organospecific, 1,2-dimethylhydrazine-induced murine tumor model was used to test the effects on tumor formation of the following dietary supplements: (1) ascorbic acid, 7% per weight; (2) alpha tocopherol, 1% per weight; (3) beta carotene, 1% per weight; and (4) canthazanthin, 1% per weight. Following a four-week dietary acclimation, a 16-week 1,2-dimethylhydrazine induction, and a four-week hiatus, the animals were killed, underwent autopsies, and tumor formation was recorded. The antioxidant supplements of ascorbic acid and alpha tocopherol resulted in a significant decrease in tumor formation when compared with control groups. In contrast, the beta carotene group showed no difference in tumor formation, and canthazanthin, a non-provitamin A carotenoid, resulted in an increase in tumor formation when compared with controls. In addition, the K-gel powder control diet (a carrier medium for alpha tocopherol acetate) had a significantly higher rate of tumor formation than the regular chow and placebo beadlet control diets. In sum, ascorbic acid and alpha tocopherol demonstrated a clear chemopreventive effect, whereas beta carotene had no effect, and canthazanthin appeared to function as a promoter in this organospecific tumor model. (Arch Surg 1989;124:217-221) References 1. Silverberg E: Cancer statistics 1988 . CA 1988;38:5-22. 2. Enstrom JE: Assessing human epidemiologic data on diet as an etiologic factor in cancer development . Bull NY Acad Med 1982;58:313-322. 3. Bruce WR, Varghesse AJ, Furrer R, et al: A mutagen in the feces of normal humans , in Hiatt HH, Watson JD, Winston JA (eds): Origins of Human Cancer . Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1977, pp 1641-1646. 4. McCann J, Ames BN: Detection of carcinogens as mutagens in the salmonella/microsome test . Proc Natl Acad Sci USA 1976;73:950.Crossref 5. Hendricks DG, Cornforth DP, Bartholomew DT, et al: Influence of dietary fiber and method of meat cookery upon human fecal microflora and mutagenicity of stool extracts. Read before the First Conference of Radioprotectors and Anticarcinogens, Gaithersberg, Md, June 21-24, 1982. 6. Mower HL, Ichinotsubo D, Wang LW, et al: Fecal mutagens in two Japanese populations with different colon cancer risks . Cancer Res 1982;42:1164-1169. 7. Wilkins TD, Lederman M, VanTassell AL, et al: Characterization of a mutagenic bacterial product in human feces . Am J Clin Nutr 1980;33:2513-2520. 8. Colten T: Statistics in Medicine . Boston, Little Brown & Co Inc, 1975, pp 99-150. 9. Colacchio TA, Memoli VA: Chemoprevention of colorectal neoplasms . Arch Surg 1986;121:1421-1424.Crossref 10. Wattenberg LW, Lam LKT, Loub WD, et al: Inhibitors of chemical carcinogenesis , in Hiatt HH, Watson JD, Winston JA (eds): Origins of Human Cancer . Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1977, pp 785-789. 11. Krinsky NI, Deneke SM: Interaction of oxygen and oxy-radicals with carotenoids . JNCI 1982;61:201-209. 12. Soloway MS, Cohen SM, de Kernion JB, et al: Failure of ascorbic acid to inhibit FANFT-induced bladder cancer . J Urol 1974;113:483-486. 13. Reddy BS, Hiroto N, Katayame S: Effect of dietary sodium ascorbate on 1,2-dimethylhydrazine or methylnitrosourea induced colon carcinogenesis in rats . Carcinogenesis 1982;3:1097-1099.Crossref 14. Dunham WB, Zuckerhandle E, Reynolds R, et al: Effects of intake of L-ascorbic acid on the incidence of dermal neoplasms induced in mice by ultraviolet light . Proc Nati Acad Sci USA 1982;79:7532-7536.Crossref 15. Abul-Hajj YJ, Kelliher M: Failure of ascorbic acid to inhibit growth of transplantable and dimethylbenzanthracene induced rat mammary tumors . Cancer Lett 1982;17:67-73.Crossref 16. Fukushima S, Imaida K, Sakata T, et al: Promoting effects of sodium L-ascorbate on two-stage urinary bladder carcinogenesis in rats . Cancer Res 1983;43:4454-4457. 17. Khar'Kovaskaya NA, Khrustalev SA, Zharova El, et al: Effect of ascorbic acid on carcinogenicity of p-hydroxyphenylacetic acid . Bull Eksp Biol Med 1982;93:64-66. 18. Mirvish SS, Wallcave L, Eagen M, et al: Ascorbate-nitrate reaction: Possible means of blocking the formation of N-nitroso compounds . Science 1972;177:65-68.Crossref 19. Fukushima S, Hagiwara A, Ogiso T, et al: Promoting effects of various chemicals in rat urinary bladder carcinogenesis . Food Chem Toxicol 1983;21:59-68.Crossref 20. Jones FE, Komorowski FA, Condon RE: Chemoprevention of 1,2-dimethylhydrazine induced large bowel neoplasms . Surg Forum 1981;31: 435-437. 21. Tsuda H, Sakata T, Shirai T, et al: Modification of MNU initiated carcinogenesis in the rat by subsequent treatment with antioxidants, phenobarbital, and ethinyl estradiol . Cancer Lett 1984;24:19-27.Crossref 22. Cook MG, McNamara P: Effects of vitamin E on dimethylhydrazine induced colonic tumors in mice . Cancer Res 1980;40:1329-1331. 23. Smalls E, Patterson RM: Reduction of benzo(a)pyrene induced chromosomal aberrations by DL-alpha-tocopherol . Eur J Cell Biol 1982;28:92-97. 24. Shklar G: Oral mucosal carcinogenesis in hamsters: Inhibition by vitamin E . JNCI 1982;5:791-793. 25. Toth P, Kashinath P: Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine hydrochloride . JNCI 1983;6:1107-1111. 26. Horvath P, Ip C: Synergistic effect of vitamin E and selenium in the chemoprevention of mammary carcinogenesis in rats . Cancer Res 1983;43: 5335-5341. 27. Odukoya 0, Hawach F, Shklar G: Retardation of experimental oral cancer by topical vitamin E . Nutr Cancer 1984;6:98-104.Crossref 28. Ip C: Dietary vitamin E intake and mammary carcinogenesis in rats . Carcinogenesis 1982;3:1453-1456.Crossref 29. Shamberger RJ: Relationship of selenium to cancer . JNCI 1970;44: 931-936. 30. Seifter E, Rettura G, Padawer J, et al: Maloney murine sarcoma virus tumors in cba/j mice: Chemoprevention and chemotherapeutic actions of supplemental beta-carotene . JNCI 1982;68:835-840. 31. Mathews-Roth MM: Antitumor activity of beta-carotene, canthaxanthine and phytoene . Oncology 1982;39:33-37.Crossref 32. Rettura G, Stratford F, Levenson SM, et al: Prophylactic and therapeutic actions of supplemental beta-carotene in mice inoculated with C3HBA adenocarcinoma cells: Lack of therapeutic action of supplemental ascorbic acid . JNCI 1982;59:73-77. 33. Seifter E, Rettura G, Padawer J, et al: Regression of C3HBA mouse tumor due to X-ray therapy combined with supplemental beta-carotene or vitamin A . JNCI 1983;71:409-417. 34. Alam SQ, Alam BS: Chemopreventive effects of beta-carotene and 13-cis-retinoic acid on salivary gland tumors . Fed Proc 1983;42:1313. 35. Santamaria L, Bianchi A, Arnaboldi A, et al: Dietary carotenoids block photocarcinogenic enhancement by benzo(a)pyrene and inhibit its carcinogenesis in the dark . Experientia 1983;39:1043-1045.Crossref 36. Santamaria L, Bianchi A, Arnaboldi A, et al: Prevention of the benzo(a)pyrene photocarcinogenic effect by beta-carotene and canthaxanthine: Preliminary study . Boll Chim Farm 1980;119:745-748. 37. Epstein JH: Effects of beta-carotene on ultraviolet induced cancer formation in the hairless mouse skin . Photochem Photobiol 1977;25:211-213.Crossref 38. Goerz G, Ippen H: Treatment of photodermatoses with carotenoids . Dtsch Med Wochenschr 1977;102:1051-1055.Crossref 39. Goerz G: Erythropoietic protoporphyria . Fortschr Med 1979;97:1625-1630. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Antioxidants vs Carotenoids: Inhibitors or Promoters of Experimental Colorectal Cancers

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References (54)

Publisher
American Medical Association
Copyright
Copyright © 1989 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1989.01410020091014
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Abstract

Abstract • The organospecific, 1,2-dimethylhydrazine-induced murine tumor model was used to test the effects on tumor formation of the following dietary supplements: (1) ascorbic acid, 7% per weight; (2) alpha tocopherol, 1% per weight; (3) beta carotene, 1% per weight; and (4) canthazanthin, 1% per weight. Following a four-week dietary acclimation, a 16-week 1,2-dimethylhydrazine induction, and a four-week hiatus, the animals were killed, underwent autopsies, and tumor formation was recorded. The antioxidant supplements of ascorbic acid and alpha tocopherol resulted in a significant decrease in tumor formation when compared with control groups. In contrast, the beta carotene group showed no difference in tumor formation, and canthazanthin, a non-provitamin A carotenoid, resulted in an increase in tumor formation when compared with controls. In addition, the K-gel powder control diet (a carrier medium for alpha tocopherol acetate) had a significantly higher rate of tumor formation than the regular chow and placebo beadlet control diets. In sum, ascorbic acid and alpha tocopherol demonstrated a clear chemopreventive effect, whereas beta carotene had no effect, and canthazanthin appeared to function as a promoter in this organospecific tumor model. (Arch Surg 1989;124:217-221) References 1. Silverberg E: Cancer statistics 1988 . CA 1988;38:5-22. 2. Enstrom JE: Assessing human epidemiologic data on diet as an etiologic factor in cancer development . Bull NY Acad Med 1982;58:313-322. 3. Bruce WR, Varghesse AJ, Furrer R, et al: A mutagen in the feces of normal humans , in Hiatt HH, Watson JD, Winston JA (eds): Origins of Human Cancer . Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1977, pp 1641-1646. 4. McCann J, Ames BN: Detection of carcinogens as mutagens in the salmonella/microsome test . Proc Natl Acad Sci USA 1976;73:950.Crossref 5. Hendricks DG, Cornforth DP, Bartholomew DT, et al: Influence of dietary fiber and method of meat cookery upon human fecal microflora and mutagenicity of stool extracts. Read before the First Conference of Radioprotectors and Anticarcinogens, Gaithersberg, Md, June 21-24, 1982. 6. Mower HL, Ichinotsubo D, Wang LW, et al: Fecal mutagens in two Japanese populations with different colon cancer risks . Cancer Res 1982;42:1164-1169. 7. Wilkins TD, Lederman M, VanTassell AL, et al: Characterization of a mutagenic bacterial product in human feces . Am J Clin Nutr 1980;33:2513-2520. 8. Colten T: Statistics in Medicine . Boston, Little Brown & Co Inc, 1975, pp 99-150. 9. Colacchio TA, Memoli VA: Chemoprevention of colorectal neoplasms . Arch Surg 1986;121:1421-1424.Crossref 10. Wattenberg LW, Lam LKT, Loub WD, et al: Inhibitors of chemical carcinogenesis , in Hiatt HH, Watson JD, Winston JA (eds): Origins of Human Cancer . Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1977, pp 785-789. 11. Krinsky NI, Deneke SM: Interaction of oxygen and oxy-radicals with carotenoids . JNCI 1982;61:201-209. 12. Soloway MS, Cohen SM, de Kernion JB, et al: Failure of ascorbic acid to inhibit FANFT-induced bladder cancer . J Urol 1974;113:483-486. 13. Reddy BS, Hiroto N, Katayame S: Effect of dietary sodium ascorbate on 1,2-dimethylhydrazine or methylnitrosourea induced colon carcinogenesis in rats . Carcinogenesis 1982;3:1097-1099.Crossref 14. Dunham WB, Zuckerhandle E, Reynolds R, et al: Effects of intake of L-ascorbic acid on the incidence of dermal neoplasms induced in mice by ultraviolet light . Proc Nati Acad Sci USA 1982;79:7532-7536.Crossref 15. Abul-Hajj YJ, Kelliher M: Failure of ascorbic acid to inhibit growth of transplantable and dimethylbenzanthracene induced rat mammary tumors . Cancer Lett 1982;17:67-73.Crossref 16. Fukushima S, Imaida K, Sakata T, et al: Promoting effects of sodium L-ascorbate on two-stage urinary bladder carcinogenesis in rats . Cancer Res 1983;43:4454-4457. 17. Khar'Kovaskaya NA, Khrustalev SA, Zharova El, et al: Effect of ascorbic acid on carcinogenicity of p-hydroxyphenylacetic acid . Bull Eksp Biol Med 1982;93:64-66. 18. Mirvish SS, Wallcave L, Eagen M, et al: Ascorbate-nitrate reaction: Possible means of blocking the formation of N-nitroso compounds . Science 1972;177:65-68.Crossref 19. Fukushima S, Hagiwara A, Ogiso T, et al: Promoting effects of various chemicals in rat urinary bladder carcinogenesis . Food Chem Toxicol 1983;21:59-68.Crossref 20. Jones FE, Komorowski FA, Condon RE: Chemoprevention of 1,2-dimethylhydrazine induced large bowel neoplasms . Surg Forum 1981;31: 435-437. 21. Tsuda H, Sakata T, Shirai T, et al: Modification of MNU initiated carcinogenesis in the rat by subsequent treatment with antioxidants, phenobarbital, and ethinyl estradiol . Cancer Lett 1984;24:19-27.Crossref 22. Cook MG, McNamara P: Effects of vitamin E on dimethylhydrazine induced colonic tumors in mice . Cancer Res 1980;40:1329-1331. 23. Smalls E, Patterson RM: Reduction of benzo(a)pyrene induced chromosomal aberrations by DL-alpha-tocopherol . Eur J Cell Biol 1982;28:92-97. 24. Shklar G: Oral mucosal carcinogenesis in hamsters: Inhibition by vitamin E . JNCI 1982;5:791-793. 25. Toth P, Kashinath P: Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine hydrochloride . JNCI 1983;6:1107-1111. 26. Horvath P, Ip C: Synergistic effect of vitamin E and selenium in the chemoprevention of mammary carcinogenesis in rats . Cancer Res 1983;43: 5335-5341. 27. Odukoya 0, Hawach F, Shklar G: Retardation of experimental oral cancer by topical vitamin E . Nutr Cancer 1984;6:98-104.Crossref 28. Ip C: Dietary vitamin E intake and mammary carcinogenesis in rats . Carcinogenesis 1982;3:1453-1456.Crossref 29. Shamberger RJ: Relationship of selenium to cancer . JNCI 1970;44: 931-936. 30. Seifter E, Rettura G, Padawer J, et al: Maloney murine sarcoma virus tumors in cba/j mice: Chemoprevention and chemotherapeutic actions of supplemental beta-carotene . JNCI 1982;68:835-840. 31. Mathews-Roth MM: Antitumor activity of beta-carotene, canthaxanthine and phytoene . Oncology 1982;39:33-37.Crossref 32. Rettura G, Stratford F, Levenson SM, et al: Prophylactic and therapeutic actions of supplemental beta-carotene in mice inoculated with C3HBA adenocarcinoma cells: Lack of therapeutic action of supplemental ascorbic acid . JNCI 1982;59:73-77. 33. Seifter E, Rettura G, Padawer J, et al: Regression of C3HBA mouse tumor due to X-ray therapy combined with supplemental beta-carotene or vitamin A . JNCI 1983;71:409-417. 34. Alam SQ, Alam BS: Chemopreventive effects of beta-carotene and 13-cis-retinoic acid on salivary gland tumors . Fed Proc 1983;42:1313. 35. Santamaria L, Bianchi A, Arnaboldi A, et al: Dietary carotenoids block photocarcinogenic enhancement by benzo(a)pyrene and inhibit its carcinogenesis in the dark . Experientia 1983;39:1043-1045.Crossref 36. Santamaria L, Bianchi A, Arnaboldi A, et al: Prevention of the benzo(a)pyrene photocarcinogenic effect by beta-carotene and canthaxanthine: Preliminary study . Boll Chim Farm 1980;119:745-748. 37. Epstein JH: Effects of beta-carotene on ultraviolet induced cancer formation in the hairless mouse skin . Photochem Photobiol 1977;25:211-213.Crossref 38. Goerz G, Ippen H: Treatment of photodermatoses with carotenoids . Dtsch Med Wochenschr 1977;102:1051-1055.Crossref 39. Goerz G: Erythropoietic protoporphyria . Fortschr Med 1979;97:1625-1630.

Journal

Archives of Surgery – American Medical Association

Published: Feb 1, 1989

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