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Genetically Mediated Responses of Microsomal Ethanol Oxidation in Mice

  • Dennis R. Petersen
  • Neal Atkinson

Abstract

Long-sleep (LS) and Short-sleep (SS) male mice were treated chronically with alcohol for 30 days. Ethanol treated mice were withdrawn from alcohol diet at 8, 12, 16, 20, 24 and 30 days of treatment for the assessment of metabolic tolerance and numerous parameters associated with the microsomal cytochrome P-450 complex. Up to 20 days of ethanol treatment, LS and SS mice displayed nearly the same enhancement of in vivo ethanol elimination rates. At 24 and 30 days of ethanol treatment, LS mice were found to have significantly greater ethanol elimination rates than SS mice chronically treated with alcohol. The induction of microsomal cytochrome P-450 content and microsomal ethanol oxidation paralleled the acquisition of metabolic tolerance with LS mice displaying significantly greater values of both microsomal parameters at 24 and 30 days of treatment. Aniline hydroxylase was maximally induced (2.5 fold) in both LS and SS mice by 16 days of treatment. Chronic ethanol treatment resulted in a significant induction of ethylmorphine and benzphetamine N-demethylase activity in both LS and SS mice with the SS selected line showing a greater (P<.05) maximal induction. These data are suggestive that the induction of MEOS may have some significance in the acquisition of metabolic tolerance to ethanol and that there may be a genetic predisposition for these adaptive responses.

Keywords

Chronic Ethanol Ethanol Treatment Ethanol Administration Chronic Alcohol Ingestion Aniline Hydroxylase 
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. Bleyman, M. A. and Thurman, R. G., 1979, Comparison of acute and chronic ethanol administration on rates of ethanol elimination in the rat in vivo, Biochem. Pharm., 28: 2027.PubMedCrossRefGoogle Scholar
  2. Chung, L. W. K., Raymond, G. and Fox, S., 1975, Role of neonatal androgen in the development of hepatic microsomal drug metabolizing enzymes, J. Pharmacol. Exp. Ther., 146: 225.Google Scholar
  3. DeCarli, L. M. and Lieber, C. S., 1967, Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet, J. Nutr., 91: 331.Google Scholar
  4. Gornall, A. G., Bardawill, C. J. and David, M. M., 1949, Determination of serum proteins by means of the biuret reaction, J. Biol. Chem., 247: 1125.Google Scholar
  5. Imai, Y., Ito, R. and Sato, J., 1966, Evidence for biochemically different types of visides in the hepatic microsomal fraction, J. Biochem., ( Japan ), 60: 417.PubMedGoogle Scholar
  6. Ioannides, C. and Parke, D. V., 1973, The effect of ethanol administration on drug oxidations and possible mechanisms of ethanol-barbiturate interactions, Biochem. Soc. Trans., 1: 716.Google Scholar
  7. Iseri, O. A., Lieber, C. S. and Gottlieb, L. S., 1966, The ultra-structure of fatty liver induced by prolonged ethanol ingestion, Am. J. Path., 48: 535.PubMedGoogle Scholar
  8. Joly, J. G., Ishii, H., Teschke, R., Hasumura, Y. and Lieber, C. S., 1973, Effect of chronic ethanol feeding on the activities and submicrosomal distribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase and the demethylases for aminopyrene and ethylmorphine, Biochem. Pharmacol., 22: 1532.PubMedCrossRefGoogle Scholar
  9. Korsten, M. A., Matsuzaki, S., Feinman, L. and Lieber, C. S., 1975, High blood acetaldehyde levels after ethanol administration in alcoholics, N. Engl. J. Med., 292: 386.PubMedCrossRefGoogle Scholar
  10. Lieber, C. S. and DeCarli, L. M., 1970, Hepatic microsomal ethanol-oxidizing system: in vitro characteristics and adaptive properties in vivo, J. Biol. Chem., 245: 2505.PubMedGoogle Scholar
  11. Lieber, C. S. and DeCarli, L. M., 1972, The role of the hepatic microsomal ethanol oxidizing system ( MEOS) for ethanol metabolism in vivo, J. Pharmacol. Exp. Therap., 181: 279.Google Scholar
  12. McClearn, G. E., Wilson, J. R. and Meredity, W., 1970, Contributions to Behavior-Genetic Analysis: The Mouse As A PrototypeGoogle Scholar
  13. G. Lindzey, G. G. Lindsey and D. D. Thiessen, eds., Appleton-Century Crofts, New York.Google Scholar
  14. Mendelson, J. H., 1968, Ethanol-1-14C metabolism in alcoholics and non-alcoholics, Science, 159: 319.PubMedCrossRefGoogle Scholar
  15. Mezey, E., 1972, Duration of the enhanced activity of the microsomal ethanol-oxidizing enzyme system and rate of ethanol degradation in ethanol-fed rats after withdrawal, Biochem. Pharmacol., 21: 137.PubMedCrossRefGoogle Scholar
  16. Mezey, E. and Tobon, F., 1971, Rates of ethanol clearance and activities of the ethanol oxidizing enzyme in chronic alcoholic patients, Gastroenterology, 61: 707.PubMedGoogle Scholar
  17. Misra, P. S., Lefevre, A., Ishii, H., Rubin, E. and Lieber, C. S., 1971, Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and rats, Am. J. Med., 18: 227.Google Scholar
  18. Miwa, G. T., Levin, W., Thomas, P. E. and Lu, A. Y. H., 1978, The direct oxidation of ethanol by a catalase and alcohol dehydrogenase free reconstituted system containing cytochrome P-450, Arch. Biochem. Biophys., 187: 464.PubMedCrossRefGoogle Scholar
  19. Ohnishi, K. and Lieber, C. S., 1977, Reconstitution of microsomal ethanol-oxidizing system, J. Biol. Chem., 252: 7124.PubMedGoogle Scholar
  20. Omura, T. and Sato, R., 1964, The carbon monoxide binding pigment of liver microsomes, I. Evidence for its hemoprotein nature, J. Biol. Chem., 239: 2370.PubMedGoogle Scholar
  21. Orrenius, S., 1965, On the mechanism of drug hydorxylation in rat liver microsomes, J. Cell. Biol., 26: 713.PubMedCrossRefGoogle Scholar
  22. Petersen, D. R., Collins, A. C. and Deitrich, R. A., 1977, Role of liver cytosolic aldehyde dehydrogenase isoenzymes in control of blood acetaldehyde concentrations, J. Pharmacol. Exp. Ther., 201: 471.PubMedGoogle Scholar
  23. Thurman, R. G., McKenna, W. R., Brentzel, H. J. and Hesse, S, 1975, Significant pathways of hepatic ethanol metabolism, Fed. Proc., 34: 11.Google Scholar
  24. Wendell, G. D. and Thurman, R. G., 1979, Effect of ethanol concentration on rates of ethanol elimination in normal and alcohol treated rats in vivo, Biochem. Pharmacol., 28: 273.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Dennis R. Petersen
    • 1
  • Neal Atkinson
    • 1
  1. 1.University of Colorado Alcohol Research CenterUSA

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