Multiplicity of Cytochrome P-450 in Morris Hepatoma

  • Minro Watanabe
  • Tetsuo Ohmachi
  • Ikuko Sagami
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


In many hepatic tumors the reduced activities of benzo[a]pyrene (BP) hydroxylase or drug-metabolizing enzymes were observed, when compared to the enzyme activities in normal adult liver, from which hepatic tumor was originated (Adamson and Fouts, 1961). Conney et al. (1957) described the remarkable and now widely recognized induction of BP hydroxylase activity in rat liver by the prior administration of BP itself, or 3-methylcholanthrene (MC), or other polycyclic hydrocarbons. An apparent induction of the drug-metabolizing enzymes by an inducer, such as MC or phenobarbital (PB), was also demonstrated in some lines of “slow-growing” Morris hepatoma (Conney and Burns, 1963; Hart et al., 1965; Watanabe et al., 1970, 1975a, 1975b), but not in Morris hepatoma 7777 (Miyake et al., 1974), Novikoff hepatoma (Hart etal., 1965), and some lines of Yoshida ascites hepatoma (Sugimura et al., 1966), all of which were considered as lines of rapidly growing tumors (Morris,1972). It was then observed that the activity and the inducibility by inducers of the drug-metabolizing enzymes were roughly correlated with the growth rate of the tumor in the host. On the other hand, very low activities of some of the drug-metabolizing enzymes were detected in the liver from newborn and fetal animals, compared with those in the liver from the corresponding adult animals (Hart et al., 1962; Watanabe et al., 1970). The inducibility of BP hydroxylation enzyme sometimes appears to be a determinant factor among those which affect the sensitivity of animals to chemical carcinogens (Watanabe et al., 1975; Nebert et al., 1978).


Polycyclic Hydrocarbon Aryl Hydrocarbon Hydroxylase Reconstituted System Morris Hepatoma Hydroxyapatite Column 
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.

Abbreviations used










Cytochrome P-450

NADPH-P-450 reductase

NADPH-Cytochrome P-450 (Cytochrome c) reductase


Potassium phosphate


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamson, R. H., and Fouts, J. R., 1961, The metabolism of drugs by hepatic tumors, Cancer Res., 21:667.Google Scholar
  2. Conney, A. H., and Burns, J. J., 1963, Induced synthesis of oxidative enzymes in liver microsomes by polycyclic hydrocarbons and drugs, Adv. Enzyme Regulation 1:189.CrossRefGoogle Scholar
  3. Conney, A. H., Miller, E. C., and Miller, J. A., 1957, Substrate induced synthesis and other properties of benzpyrene hydroxylase in rat liver, J. Biol. Chem., 228:753.PubMedGoogle Scholar
  4. Domin, B. A., Serabjit-Singh, C. J., Vanderslice, R. R., Devereux, T. R., Fouts, J. R., Bend, J. R., and Philpot, R. M., 1984, Tissue and cellular differences in the expression of cytochrome P-450 isozymes, in: “Proceeding of 9th International Congress of Pharmacology,” W. Paton, J. Mitchell and P. Turner, eds., Vol. 3, p. 219, Macmillan Press, London.Google Scholar
  5. Fennell, P. M., and Strobel, H. V., 1982, Preparation of homogeneous NADPHcytochrome P-450 reductase from rat hepatoma, Biochem. Biophys. Acta 709:173.PubMedCrossRefGoogle Scholar
  6. Gelboin, H. V., 1969, A microsome-dependent binding of benzo[a]pyrene to DNA, Cancer Res., 29:1272.PubMedGoogle Scholar
  7. Goldstein, J. A., and Linko, P., 1984, Differential induction of two 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible forms of cytochrome P-450 in extrahepatic versus hepatic tissues, Mol. Pharmacol., 25:185.PubMedGoogle Scholar
  8. Guengerich, F. P., 1978, Separation and purification of multiple forms of microsomal cytochromes P-450. Partial characterization of three apparently homogeneous cytochromes P-450 isolated from liver microsomes of phenobarbital and 3-methylcholanthrene-treated rats, J. Biol. Chem., 253:7931.PubMedGoogle Scholar
  9. Harada, N., and Omura, T., 1981, Selective induction of two different molecular species of cytochrome P-450 by phenobarbital and 3-methylcholanthrene, J. Biochem., 89:237.PubMedGoogle Scholar
  10. Hart, L. G., Adamson, R. H., Dixon, R. C., and Fouts, J. R., 1962, Stimulation of hepatic microsomal drug metabolism in the newborn and fetal rabbit, J. Pharmacol. Exptl. Therap., 137:103.Google Scholar
  11. Hart, L. G., Adamson, R. H., Morris, H. P., and Fouts, J. R., 1965, The stimulation of drug metabolism in various rat hepatomas, J. Pharmacol. Exptl. Therap., 149:7.Google Scholar
  12. Imai, Y., 1976, The use of 8-aminooctyl Sepharose for the separation of some components of the hepatic microsomal electron transfer system, J. Biochem., 80:365.Google Scholar
  13. Kusunose, E., Ogita, K., Ichihara, K., and Kusunose, M., 1981, Effect of cytochrome b5 on fatty acid co-and (w-1)-hydroxylation catalyzed by partially purified cytochrome P-450 from rabbit kidney cortex microsomes, J. Biochem., 90:1069.PubMedGoogle Scholar
  14. Miller, E. C., and Miller, J. A., 1966, Mechanisms of chemical carcinogenesis: Nature of proximate carcinogens and interactions with macromolecules, Pharmacol. Rev., 18:805.PubMedGoogle Scholar
  15. Miyake, Y., Gaylor, J. L., and Morris, H. P., 1974, Abnormal microsomal cytochromes and electron transport in Morris hepatoma, J. Biol. Chem., 249:1980.Google Scholar
  16. Morris, H. P., 1972, Isozymes in selected hepatomas and some biological characteristics of a spectrum of transplantable hepatomas, in “Isozymes and Enzyme Regulation in Cancer,” S. Weinhouse, and T. Ono, eds., p. 95, Univ. Tokyo Press, Tokyo.Google Scholar
  17. Nebert, D. W., Atlas, S. A., Guenthner, T. M., and Kouri, R. E., 1978, The Ah locus: genetic regulation of the enzymes which metabolize polycyclic hydrocarbons and the risk for cancer, in: “Polycyclic Hydrocarbons and Cancer,” H. V. Gelboin and P.O.P. Ts’o, eds., Vol. 2, p. 345, Academic Press, New York.Google Scholar
  18. Negishi, M., and Nebert, D. W., 1979, Structural gene products of the “Ah” locus: genetic and inirnunochemical evidence for two forms of mouse liver cytochrome P-450 induced by 3-methylcholanthrene, J. Biol. Chem., 254: 11015.PubMedGoogle Scholar
  19. Ohmachi, T., Sagami, I., Fujii, H., and Watanabe, M., 1985, Microsomal monooxygenase system in Morris hepatoma: purification and characterization of cytochrome P-450 from Morris hepatoma 5123D of 3-methylcholanthrene-treated rats, Arch. Biochem. Biophys., 236:176.PubMedCrossRefGoogle Scholar
  20. Ryan, D. E., Thomas, P. E., Korzeniowski, D., and Levin, W., 1979, Separation and characterization of highly purified forms of liver microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls, phenobarbital, and 3-methylcholanthrene, J. Biol. Chem., 254:1365.PubMedGoogle Scholar
  21. Sagami, I., and Watanabe, M., 1983, Purification and characterization of pulmonary cytochrome P-450 from 3-methylcholanthrene-treated rats, J. Biochem., 93:1499.PubMedGoogle Scholar
  22. Saine, S. E., and Strobel, H. W., 1976, Drug metabolism in liver and tumors. Resolution of components and reconstitution of activity, Mol.Pharmacol., 12:649.PubMedGoogle Scholar
  23. Strobel, H. W., Digman, J. D., Saine, S. E., Fang, W.-F., and Fennell, P. M., 1978, The drug metabolism systems of liver and liver tumors:A comparison of activities and characteristics, Mol. Cell. Biochem., 22:79.PubMedCrossRefGoogle Scholar
  24. Sugimura, T., Ikeda, K., Hirota, K., Hozumi, M., and Morris, H. P., 1966, Chemical, enzymatic, and cytochrome assays of microsomal fraction of hepatoma with different growth rates, Cancer Res., 26:1711.PubMedGoogle Scholar
  25. Vatsis, K. P., Theoharides, A. D., Kupfer, D., and Coon, M. J., 1982, Hydroxylation of prostaglandins by inducible isozymes of rabbit liver microsomal cytochrome P-450. Participation of cytochrome b5, J. Biol. Chem., 257:11221.PubMedGoogle Scholar
  26. Wada, A., Okamoto, M., Nonaka, Y., and Yamano, T., 1984, Aldosterone biosynthesis by a reconstituted cytochrome P-45011ß system, Biochem. Biophys. Res. Commun., 119:365.PubMedCrossRefGoogle Scholar
  27. Watanabe, M., Konno, K., and Sato, H., 1975a, Aryl hydrocarbon hydroxylase in Morris hepatoma 5123D, Gann, Jpn. J. Cancer Res., 66:499.Google Scholar
  28. Watanabe, M., Konno, K., and Sato, H., 1975b, Properties of aryl hydrocarbon hydroxylase in microsomes of Morris hepatoma 5123D and the host liver, Gann, Jpn. J. Cancer Res., 66:505.Google Scholar
  29. Watanabe, M., Potter, V. R., and Morris, H. P., 1970, Benzpyrene hydroxylase activity and its induction by methylcholanthrene in Morris hepatomas, in host livers, in adult livers, and in rat liver during development, Cancer Res., 30:263.PubMedGoogle Scholar
  30. Watanabe, M., Sagami, I., Ohmachi, T., and Fujii, H., 1985, Characteristics of purified cytochrome P-450s in microsomes of rat lung and Morris hepatoma 5123D, in: “P-450 and Chemical Carcinogenesis,” Y. Tagashira and T. Omura, eds., p. 19, Plenum Press, New York.CrossRefGoogle Scholar
  31. Watanabe, M., Watanabe, K., Konno, K., and Sato, H., 1975, Genetic differences in the induction of aryl hydrocarbon hydroxylase and benzo[a]pyrene carcinogenesis in C3H/He and DBA/2 strains of mice, Gann, Jpn. J. Cancer Res., 66:217.Google Scholar
  32. Weisburger, J. H., and Weisburger, E. K., 1973, Biochemical formation and pharmacological, toxicological, and pathological properties of hydroxylamines and hydroxamic acids, Pharmacol. Rev., 25:1.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Minro Watanabe
    • 1
  • Tetsuo Ohmachi
    • 1
  • Ikuko Sagami
    • 1
  1. 1.Research Institute for Tuberculosis and CancerTohoku UniversitySendai, 980Japan

Personalised recommendations