Abstract
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 ℓ D ℓ E − grc) and BY1 (RT1.A ℓ B ℓ D ℓ 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.
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References
H. C. Pitot, Neoplasia: A somatic mutation or heritable change in cytoplasmic membranes, J. Natl. Cancer Inst. 53:905 (1974).
W. T. London, Primary hepatocellular carcinoma: Etiology, pathogenesis and prevention, Hum. Pathol. 12:1085 (1981).
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).
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).
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).
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).
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).
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).
R. Schulte-Herman, Tumor promotion in the liver, Arch. Toxicol. 57:147 (1985).
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).
K. N. Rao, Regulatory aspects of cholesterol metabolism in cells with different degrees of replication, Toxicol. Pathol. 14:430 (1986).
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).
P. Beaconsfield, R. Rainsbury and G. Kalton, Glucose-6-phosphate dehydrogenase deficiency and the incidence of cancer, Oncologia 19:11 (1965).
S. N. Naik and D. E. Anderson, The association between glucose-6-phosphate dehydrogenase deficiency and cancer in American Negroes, Oncology 25:356 (1971).
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).
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).
Worthington Enzyme Manual, Worthington biochemical Corporation, Freehold, New Jersey, pp. 212 (1979).
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).
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).
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).
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).
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).
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Melhem, M.F., Rao, K.N., Kunz, H.W., Gill, T.J. (1988). Susceptibility of grc-Bearing Rats to DEN and Its Relationship to the HMP Pathway. In: Feo, F., Pani, P., Columbano, A., Garcea, R. (eds) Chemical Carcinogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9640-7_54
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DOI: https://doi.org/10.1007/978-1-4757-9640-7_54
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