Susceptibility of grc-Bearing Rats to DEN and Its Relationship to the HMP Pathway

  • Mona F. Melhem
  • Kalipatnapu N. Rao
  • Heinz W. Kunz
  • Thomas J. GillIII


The genetic factors underlining the susceptibility to cancer have been examined in a number of experimental1 and clinical2 settings, and there is substantial evidence for the existence of such factors. Studies in both rats3 and mice4 have provided evidence that genes linked to the major histocompatibility complex (MHC) play an important role in the susceptibility to cancer following exposure to chemical carcinogens. Previously, we3 showed that two strains that differ in their MHC’s (RT1) and in the presence of the MHC-linked growth and reproduction complex (grc) differed in their susceptibility to the chemical carcinogen N-2-acetylaminofluorene (AAF). The R10 (RT1.A n B D E grc) and BY1 (RT1.A B D E grc) strains were highly susceptible to AAF, whereas the BI (A n B a D a E u grc +) and BY2 (A u B u D u E u grc +) strains were not. These findings indicated that genes in, or linked to, the MHC were involved in the increased susceptibility to preneoplastic changes and suggest that the presence of the grc is critical in determining this susceptibility.


Major Histocompatibility Complex G6PD Deficiency Chemical Carcinogen Acinar Cell Carcinoma G6PD Activity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H. C. Pitot, Neoplasia: A somatic mutation or heritable change in cytoplasmic membranes, J. Natl. Cancer Inst. 53:905 (1974).PubMedGoogle Scholar
  2. 2.
    W. T. London, Primary hepatocellular carcinoma: Etiology, pathogenesis and prevention, Hum. Pathol. 12:1085 (1981).PubMedCrossRefGoogle Scholar
  3. 3.
    K. N. Rao, H. Shinozuka, H. W. Kunz and T. J. Gill III, Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (GRC), Int. J. Cancer 34:113 (1984).PubMedCrossRefGoogle Scholar
  4. 4.
    D. W. Nebert and N. M. Jensen, The ah locus: Genetic regulation of the metabolism of carcinogens, drugs, and other environmental chemicals by cytochrome p450-mediated monoxygenase, CRC Crit. Rev. Biochem. 6:401 (1979).PubMedCrossRefGoogle Scholar
  5. 5.
    K. N. Rao, S. Kottapally and H. Shinozuka, Acinar cell carcinoma of rat pancreas. Mechanism of deregulation of cholesterol metabolism, Toxicol. Path. 12:62 (1984).CrossRefGoogle Scholar
  6. 6.
    K. N. Rao, S. Kottapally and H. Shinozuka, Lipid composition and 3-hydroxy-3 methylglutaryl CoA reductase activity of acinar cell carcinoma of rat pancreas, Biochim. Biophys. Acta 759:74 (1983).PubMedCrossRefGoogle Scholar
  7. 7.
    P. Pani, S. Dessi, K. N. Rao, B. Batetta and E. Laconi, Changes in serum and hepatic cholesterol in lead induced liver hyperplasia, Toxicol. Pathol. 12:162 (1984).PubMedCrossRefGoogle Scholar
  8. 8.
    G. M. Ledda-Columbano, A. Columbano, S. Dessi, P. Coni, C. Chiodino and P. Pani, Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferative hepatocyte nodules, Carcinogenesis 6:1371 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    R. Schulte-Herman, Tumor promotion in the liver, Arch. Toxicol. 57:147 (1985).CrossRefGoogle Scholar
  10. 10.
    H. J. Hacker, M. A. Moore, D. Mayer and P. Bannash, Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver, Carcinogenesis 3:1265 (1982).PubMedCrossRefGoogle Scholar
  11. 11.
    K. N. Rao, Regulatory aspects of cholesterol metabolism in cells with different degrees of replication, Toxicol. Pathol. 14:430 (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    A. G. Schwartz, Inhibition of spontaneous breast cancer formation in female C3H(Avy/a) mice by long-term treatment with dehydroepiandrosterone, Cancer Res. 39:1129 (1979).PubMedGoogle Scholar
  13. 13.
    P. Beaconsfield, R. Rainsbury and G. Kalton, Glucose-6-phosphate dehydrogenase deficiency and the incidence of cancer, Oncologia 19:11 (1965).CrossRefGoogle Scholar
  14. 14.
    S. N. Naik and D. E. Anderson, The association between glucose-6-phosphate dehydrogenase deficiency and cancer in American Negroes, Oncology 25:356 (1971).PubMedCrossRefGoogle Scholar
  15. 15.
    H. Shinozuka and B. Lombardi, Synergistic effect of a choline-devoid diet and phenobarbital in promoting the emergence of foci of gammaglutamyltranspeptidase-positive hepatocytes in the liver of carcinogen-treated rats, Cancer Res. 40:3846 (1980).PubMedGoogle Scholar
  16. 16.
    K. Betke, E. Keutler, G. J. Brewer, H. N. Kirkman, L. Luzzatto, A. G. Motulsky, B. Ramst and M. Simiscalco, Standarization procedures for the study of G6PD, Report, WHO Scientific Group, WHO Tech. Rep. Ser. No. 366 (1967).Google Scholar
  17. 17.
    Worthington Enzyme Manual, Worthington biochemical Corporation, Freehold, New Jersey, pp. 212 (1979).Google Scholar
  18. 18.
    K. N. Rao, J. Tuma and B. Lombardi, Acute hemorrhagic pancreatic necrosis in mice: Intraparenchymal activation of zymogens and other enzyme changes in pancreas and serum, Gastroenterology 70:720 (1976).PubMedGoogle Scholar
  19. 19.
    H. Shinozuka, M. A. Sells, S. L. Katyal, S. Sell and B. Lombardi, Effects of choline devoid diet on the emergence of gamma-glutamyl transpeptidase positive foci in the liver of carcinogen treated rats, Cancer Res. 39:2515 (1979).PubMedGoogle Scholar
  20. 20.
    O. H. Lowry, N. J. Rosebrough, A. L. Farr and R. J. Randall, Protein measurement with folin phenol reagent, J. Biol. Chem. 193:265 (1951).PubMedGoogle Scholar
  21. 21.
    R. G. D. Steel and J. H. Torrie, “Principles and procedures of statistics: a biomedical approach”, 2nd ed., pp. 137, McGraw Hill, New York, (1980).Google Scholar
  22. 22.
    T. J. Gill III, The borderland of embryogenesis and carcinogenesis. Major histocompatibility complex-linked genes affecting development and their possible relationship to the development of cancer, Biochim. Biophys. Acta 738:93 (1984).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Mona F. Melhem
    • 1
    • 2
  • Kalipatnapu N. Rao
    • 1
    • 2
  • Heinz W. Kunz
    • 1
    • 2
  • Thomas J. GillIII
    • 1
    • 2
  1. 1.Department of PathologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.The Veterans Administration Medical CenterPittsburghUSA

Personalised recommendations