The Use of ALDH Induction as a Carcinogenic Risk Marker in Comparison with Typical in Vitro Mutagenicity System

  • V. Vasiliou
  • K. Athanasiou
  • M. Marselos


Several aldehyde-oxidizing isozymes, the aldehyde dehydrogenases (ALDHs), are distributed in the mitochondrial, the microsomal and the cytosolic fraction of the rat liver (Deitrich, 1966; Tottmar et al., 1973). Previous studies have described the induction of two cytosolic aldehyde dehydrogenases by a variety of xenobiotics (Deitrich, 1971; Deitrich et al., 1977). Phenobarbital induces a specific ALDH (PB-ALDH) in certain genetically defined rat strains (Deitrich, 1971; Marselos, 1976). In addition, another cytosolic ALDH (T-ALDH) is induced by 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD) and certain carcinogenic polycyclic aromatic hydrocarbons (P.A.Hs) in all rat strains tested (Marselos and Hanninen, 1974; Deitrich et al., 1978; Marselos et al., 1979). This isozyme is induced also in cultures of human hepatocytes, after in vitro exposure to 3-methylcholanthrene (Marselos et al., 1987).


Polycyclic Aromatic Hydrocarbon Aldehyde Dehydrogenase ALDH Activity Carcinogenic Potency Aldehyde Dehydrogenase Activity 
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  1. Allen, B., and Lindahl, R., 1982, Sequential 2-acetylaminofluorenephenobarbital exposure induces a cytosolic aldehyde dehydrogenase during rat hepatocarcinogenesis, Carcinogenesis, 3: 533.PubMedCrossRefGoogle Scholar
  2. Ames, B.N., McCann J. and Vamasaki E., 1975, Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test, Mutation Res., 31: 347.PubMedCrossRefGoogle Scholar
  3. Ames, B.N. and Hooper, K., 1978, Does carcinogenic potency correlate with mutagenic potency in the Ames assay? Areply, Nature (London), 271: 19.CrossRefGoogle Scholar
  4. Berlin, A., Draper, M., Hemminki, K., and Vainio, H., 1984, Monitoring human exposure to carcinogenic and mutagenic agents,IARC Scientific Publication’ No. 59, Lyon.Google Scholar
  5. Deitrich, R.A., 1966, Tissue and subcellular distribution of mammalian aldehyde-oxidizing capacity, Biochem. Pharmacol., 15: 1911.PubMedCrossRefGoogle Scholar
  6. Deitrich, R.A., 1971, Genetic aspects of increase in rat liver aldehyde dehydrogenase induced by phenobarbital, Science 173: 334.PubMedCrossRefGoogle Scholar
  7. Deitrich, R.A., Bludeau, P., Stock, T., and Roper, M., 1977, Induction of different rat liver supernatant aldehyde dehydrogenase by phenobarbital and tetrachlorodibenzo-p-dioxin, J. Biol. Chem., 252: 6169.PubMedGoogle Scholar
  8. Deitrich, R.A., Bludeau, P., Roper, M., and Schmuck, J., 1978, Induction of aldehyde dehydrogenase, Biochem. Pharmacol., 27: 2343.CrossRefGoogle Scholar
  9. Feinstein, R.N., and Cameron, E.C., 1972, Aldehyde dehydrogenase activity in rat hepatomas, Biochem. Biophys. Res. Commun., 48: 1140.Google Scholar
  10. Gornall, A.G., Bardawill, C.J., and David, M.M., 1949, Determination of serum proteins by means of the biuret reaction, J. Biol. Chem., 177: 751.PubMedGoogle Scholar
  11. Jones, J.D.E., Evces, S., and Lindahl, R., 1984, Expression of tumor-associated aldehyde dehydrogenase during rat hepatocarcinogenesis using the resistant hepatocyte model, Carcinogenesis, 5: 1679.PubMedCrossRefGoogle Scholar
  12. Kamath, S.A., Kummerow, F.A., and Narayan K.N., 1971, A simple procedure for the isolation of rat liver microsomes, FEBS Lett., 17: 90.PubMedCrossRefGoogle Scholar
  13. Lijinsky, W., and Reurer, M.D., 1981, Comparative carcinogenicity of some alifatic nitrosoamines in Ficher rats, Cancer Lett. 14: 297.PubMedCrossRefGoogle Scholar
  14. Lindahl, R., Roper, M., and Deitrich, R.A., 1978, Rat liver aldehyde dehydrogenase-immunochemical idendity of 2,3,7,8-tetrachlorodibenzo-pdioxin-inducible normal liver and 2-acetylaminofluorene-inducible hepatoma isozymes, Biochem. Pharmacol., 27: 2463.PubMedCrossRefGoogle Scholar
  15. Lindahl, R., 1980, Differentiation of normal and inducible rat liver aldehyde dehydrogenase by disulfiram inhibition in vitro, Biochem. Pharmacol., 29: 3026.PubMedCrossRefGoogle Scholar
  16. Lindahl, R., and Evces, S., 1984, Rat liver aldehyde dehydrogenase. II. Isolation and characterization of four inducible isozymes, J. Biol. Chem. 259: 1 1991.Google Scholar
  17. Maron, M.M., and Ames B.N., 1983, Revised methods for the mutagenicity test, Mutation Res., 113: 173.PubMedCrossRefGoogle Scholar
  18. Marselos, M., and Hänninen, O., 1974, Enhancement of D-glucuronolactone and aldehyde dehydrogenase activity in the rat liver by inducers of drug metabolism, Biochem. Pharmacol., 24: 1457.CrossRefGoogle Scholar
  19. Marselos, M., 1976, Genetic variation of drug metabolizing enzymes in the Wistar rat, Acta Pharmacol. et Toxicol., 39: 186.CrossRefGoogle Scholar
  20. Marselos, M., Törrönen, R., Koivula, T., and Koivusalo, M., 1979, Comparison of phenobarbital - and carcinogen - induced aldehyde dehydrogenase in the rat, Biochim. Biophys. Acta, 583: 110.PubMedCrossRefGoogle Scholar
  21. Marselos, M., and Michalopoulos, G., 1986, Phenobarbital enhances the aldehyde dehydrogenase activity of rat hepatocyte in vitro and in vivo,. Acta Pharmacol. et Toxicol., 59: 405.Google Scholar
  22. Marselos, M., Strom, S., and Michalopoulos, G., 1987, Effect of phenobarbital and 3-methylcholanthrene on aldehyde dehydrogenase activity in cultures of HepG2 and normal human hepatocytes, Chem. Biol. Interactions, 62: 75.CrossRefGoogle Scholar
  23. Simpson, V.J., Baker, R., and Deitrich, R.A., 1985, Inducible aldehyde dehydrogenase from rat liver cytosol, Toxicol. Appl. Pharmacol., 79: 193.PubMedCrossRefGoogle Scholar
  24. Törrönen, R., Nousiainen, U., and Marselos, M., 1980, Induction of liver aldehyde dehydrogenase activity-An indicator of chemical exposure? Abstract, Int. Congress on Toxicology, July 6–11, Brussels.Google Scholar
  25. Törrönen, R., Nousiainen, U., and Hänninen, O., 1981. Induction of aldehyde dehydrogenase by polycyclic aromatic hydrocarbons in rats, Chem. Biol. Interactions, 36: 33.CrossRefGoogle Scholar
  26. Tottmar, S.O.C., Pettersson, H., and Kiessling, K.H., 1973, The subcellular distribution and properties of aldehyde dehydrogenase in rat liver, Biochem. J., 135: 577.PubMedGoogle Scholar
  27. Wischusen, S., Evces, S., and Lindahl, R., 1982, Changes in aldehyde dehydrogenase phenotype during the promotion phase of rat hepatocarcinogenesis, Proc. Am. Assoc. Cancer Res., 23: 59.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • V. Vasiliou
    • 1
  • K. Athanasiou
    • 1
  • M. Marselos
    • 1
  1. 1.Department of Pharmacology, Medical SchoolUniversity of IoanninaIoanninaGreece

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