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A Reduction in Mixed Function Oxidases and in Tumor Promoting Effects of Ethanol in a NDEA-Initiated Hepatocarcinogenesis Model

  • Siraj I. Mufti
  • I. Glenn Sipes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)

Abstract

Epidemiologic studies associate an increased cancer risk with chronic alcohol consumption [for example, Hakulinen et al., 1974; Breslow and Enstrom, 1974; Feldman et al., 1985; Williams and Horn, 1977; Schottenfeld, 1979; Kono and Ikeda, 1979; Tnyns, 1979; Doll and Peta, 1981]. However, the experimental evidence for this association is not clear. While a number of studies indicate that ethanol, the active ingredient of alcoholic beverages, increases the incidence of chemically induced tumors [for example, Gibel, 1967; Griciute et al., 1982; Gabriel et al., 1982; McCoy et al., 1986], other studies do not show such an effect [Schmahl et al., 1965; Sehmahl, 1976; Habs and Sehmahl, 1981; Teschke et al., 1983]. We recently reported studies that showed that ethanol increased tumor incidence only when administered as a tumor promoter after treatment with an esophagus specific carcinogen, N-nitrosomethylbenzlamine (NMBzA) was completed [Mufti et al., 1989]. In these studies we wanted to determine the effect of ethanol when given as a tumor promoter on liver carcinogenesis induced by N-nitrosodiethylamine (NDEA). The paper offers an explanation for the negative results obtained in these studies.

Keywords

Ethanol Consumption Mixed Function Oxidase Chronic Alcohol Consumption Chronic Ethanol Consumption NADPH Cytochrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. American Institute of Nutrition (1977). Report of the American Institute of Nutrition Ad Hoc Committee on standards for nutritional studies. J. Nutr. 107, 1340 - 1348.Google Scholar
  2. Breslow, N.E. and Enstrom, J.E. (1974). Geographic correlations between cancer mortality rates and alcohol-tobacco consumption in the United States. J. Natl. Cancer. Inst. 53, 631 - 639.PubMedGoogle Scholar
  3. Doll, R. and Peto, R. (1981). The causes of cancer: quantitative estimates of avoidable risk of cancer in the United States today. J. Natl. Cancer. Inst. 66, 1191-1308,.PubMedGoogle Scholar
  4. Feldman, J.G., Haan, M., Nagarajen, M. and Kissin, B. (1975). A case-control investigation of alcohol, tobacco, and diet in head and neck cancer. Prey. Med. 4, 444 - 463.CrossRefGoogle Scholar
  5. Gabrial, G.N., Schrager, T.F. and Newberne, P.M. (1982). Zinc deficiency, alcohol and a retinoid: association with esophageal cancer in rat. J. Natl. Cancer Inst. 68, 785 - 789.PubMedGoogle Scholar
  6. Garcea, R., Canuto, R.A., Biocca, M.E., Muzio, G., Rossi, M.A. and Dianzani, M.U. (1984). Functional alterations of the endoplasmic reticulum and the detoxification systems during diethyl-nitrosamine carcinogenesis in rat liver. Cell Biochem. Funct. 2, 177 - 181.CrossRefPubMedGoogle Scholar
  7. Gibel, Von W. (1967). Experimental studies on syncarcinogenesis of oesophageal cancer. Arch. Geschwulstforsch 30, 181 - 189.PubMedGoogle Scholar
  8. Griciute, L., Castegnaro, M. and Bereziat, J-C. (1982). Influence of ethyl alcohol in the carcinogenic activity of N-nitrosodi-n-propylamine. In Bartsch H, Castegnaro M, O’Neill IK, Okada M and Davis W. (eds). N-Nitroso Compounds: Occurrence and Biological Effects. IARC Scientific Publication, Lyon, France, Vol. 41; pp. 643 - 648.Google Scholar
  9. Habs, M. and Schmahl, D. (1981). Inhibition of the hepatocarcinogenic activity of diethylnitrosamine (DENA) by ethanol in rats. Hepato-gastroenteroi 28, 242 - 244.Google Scholar
  10. Hakulinen, T., Lehtimaki, L., Lehtonen, M. and Teppo, L. (1974). Cancer morbidity among two male cohorts with increased alcohol consumption in Finland. J. Natl. Cancer Inst. 52, 1711 - 1714.PubMedGoogle Scholar
  11. Kono, S. and Ikeda, M. (1979). Correlation between cancer mortality and alcoholic beverage in Japan. Br. J. Cancer 40, 449 - 455.CrossRefPubMedGoogle Scholar
  12. Koop, D.R., Morgan, E.T., Tarr, G.E. and Coon, M.J. (1982). Purification and characterization of a unique isozyme of cytochrome P-450 from liver microsomes of ethanol-treated rabbits. J. Biol. Chem. 257, 8472 - 8480.PubMedGoogle Scholar
  13. Lans, M., DeGerlache, J., Taper, H.S., Preat, V. and Roberfroid, M.B. (1983). Phenobarbital as a promoter in the initiation/selection process of experimental rat hepatocarcinogenesis. Carcinogenesis 4, 141 - 144.CrossRefPubMedGoogle Scholar
  14. Lieber, C.S. and DeCarli, L.M. (1982). The feeding of alcohol in liquid diets: two decades of applications and 1982 update. Alcohol Clin. Exp. Res. 6, 523-531.CrossRefPubMedGoogle Scholar
  15. Lieber, C.S. and Savolainen, M. (1984). Ethanol and lipids. Alcohol Clin. Exp. Res. 8, 409 - 423.CrossRefGoogle Scholar
  16. Masters, B. and Okits, R.T.,, (1980). The history, properties and function of NADPH cytochrome P-450 reductase. Pharmacol. Therapeut. 9, 227 - 244.CrossRefGoogle Scholar
  17. McCoy, C.D., Hecht, S.S. and Furuya, K. (1986). The effect of chronic ethanol consumption on the tumorigenicity of N-nitrosopyrrolidine in male Syrian golden hamsters. Cancer Lett. 33, 151 - 159.CrossRefPubMedGoogle Scholar
  18. Mufti, S.I. (1989). An evaluation of currently used laboratory tests to detect alcoholism and alcohol abuse and suggestions for improvement. In: Biochemistry and Physiology of Substance Abuse (Ed. Watson RR), in press, CRC Press, Boca Raton, FL.Google Scholar
  19. Mufti, S.I., Becker, G. and Sipes, I.G. (1989). Effect of chronic dietary ethanol consumption on the initiation and promotion of chemically-induced esophageal carcinogenesis in experimental rats. Carcinogenesis 10, 303 - 309.CrossRefPubMedGoogle Scholar
  20. Mufti, S.I. (1990). Generation of free radicals in ethanol metabolism may be responsible for tumor promoting effects of ethanol. These proceedings. Omura, T. and Sato, R. (1964). The carbon monoxide-binding pigment of liver microsomes. J. Biol. Chem. 239, 2370 - 2385.Google Scholar
  21. Rutenberg, A.M., Kim, H., Frishbein, J.W., Hanker, J.S., Wasserkrug, H.L. and Seligman, A. (1969). Histochemical and ultrastructural demonstration of yglutamyl transpeptidase activity. J. Histochem. Cytochem. 17, 517 - 526.CrossRefGoogle Scholar
  22. Ryan, D.E., Koop, D.R., Thomas, P.E., Coon, M.J. and Levin, W. (1986). Evidence that isoniazed and ethanol induce the same microsomal cytochrome P-450 in rat liver, an isozyme homologous to rabbit liver cytochrome P-450 3a. Arch. Biochem. Biophys. 246, 633 - 644.Google Scholar
  23. Rayan, D.E., Ramathan, L., Lida, S., Thomas, P.E., Haniu, M., Shively, J.E., Lieber, C.S. and Levin, W. (1985). Characterization of a major form of rat hepatic cytochrome P-450 induced by isoniazid. J. Biol. Chem. 260, 6385 - 6393.Google Scholar
  24. Schmahl, D. (1976). Investigations on esophageal carcinogenicity by methyl-phenyl-nitrosamine and ethyl alcohol in rats. Cancer Lett. 1, 215 - 218.CrossRefPubMedGoogle Scholar
  25. Schmahl, D., Thomas, C., Sattler, W. and Scheid, G.F. (1965). Experimental studies of syncarcinogenesis: III. Attempts to induce cancer in rats by administering di-ethylnitrosamine and CC14 (or ethyl alcohol) simultaneously. In addition, an experimental contribution regarding ‘alcoholic cirrhosis’. Z Krebsforsch 66, 526 - 532.Google Scholar
  26. Schottenfeld, D. (1979). Alcohol is a co-factor in the etiology of cancer. Cancer 43, 1961 - 1966.CrossRefGoogle Scholar
  27. Taylor, G.F., Turrill, G.H. and Carter, G. (1984). Blood alcohol analysis: a comparison of the gas chromatographic assay with an enzyme assay. Pathology 16, 157 - 159.CrossRefPubMedGoogle Scholar
  28. Tesehke, R., Minzlaff, M., Oldiges, H. and Frenzel, H. (1983). Effect of chronic alcohol consumption on tumor incidence due to dimethylnitrosamine administration. J. Cancer Res. Clin. Oncol. 106, 58 - 64.CrossRefGoogle Scholar
  29. Tuyns, A.J. (1979). Epidemiology of alcohol and cancer. Cancer Res. 39, 2840 - 2843.PubMedGoogle Scholar
  30. Williams, R.R., and Horm, J.W. (1977). Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey. J. Natl. Cancer. Inst. 58, 525 - 547.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Siraj I. Mufti
    • 1
  • I. Glenn Sipes
    • 1
  1. 1.Department of Pharmacology and ToxicologyThe University of Arizona College of PharmacyTucsonUSA

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