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Role of Injury and Hyperplasia in the Induction of Hepatocellular Carcinoma

Stanley Goldfarb, M.D.; Frederick G. Zak, M.D.
[+] Author Affiliations

New York City

From the Department of Pathology, The Mount Sinai Hospital.


JAMA. 1961;178(7):729-731. doi:10.1001/jama.1961.73040460007007b
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THE INDUCTION of hepatocellular carcinoma is not dependent on continuous feeding of carcinogen. Short periods of exposure to carcinogen may result in tumors many weeks or months after drug withdrawal.1 Nevertheless, hepatocellular injury and hyperplasia apparently precede the development of hepatomas. The persistence, regression, or alteration of early hepatocellular injury and hyperplasia were studied in rats after withdrawal of 3'-methyl-4-dimethylamino azobenzene (methyl butter yellow, MeBY), a potent carcinogen. Since 26 days of drug feeding causes a low incidence of hepatocellular carcinoma and 40 days a high incidence of hepatomas,2 2 groups of rats fed the drug for these intervals were compared. Morphologic changes that were more prominent in the second group might be associated with hepatoma induction. The formation and persistence of nodules of hydropic, weakly basophilic cells, deficient in glucose-6-phosphatase (G-6-P' ase) that are closely associated with hepatocellular carcinoma will be described.

Materials and Methods  Sprague-Dawley male

REFERENCES

Glinos, A. D.; Bucher, N. L. R.; and Aub, J. C.:  Effect of Liver Regeneration on Tumor Formation in Rats Fed 4-Dimethylaminoazobenzene , J Exp Med 93:313-324 ( (April) ) 1951;.
Arcos, J. C.; Griffith, G. W.; and Cunningham, R. W.:  Fine Structural Alterations in Cell Particles During Chemical Carcinogenesis. 2. Further Evidence for Their involvement in Mechanism of Carcinogenesis. Swelling of Rat Liver Mitochondria During Feeding of Amino Azo Dyes . J Biophys Biochem Cytol 7:49-60 ( (Feb.) ) 1960;.
Miller, J. A., and Miller, E. C.:  Carcinogenicity of Certain Derivatives of p-Dimethylaminoazobenzene in Rat , J Exp Med 87:139-156 ( (Feb.) ) 1948;.
Wachstein, M., and Meisel, F.:  On Histochemical Demonstration of Glucose-6-Phosphatase , J Histochem Cytochem 4:592 ( (Nov.) ) 1956;.
Stewart, H. L., and Snell, K. C.:  Histopathology of Experimental Tumors of Liver of Rat , in The Psysiopathology of Cancer (Ed. 2) by Homburger, F.: New York: Hoeber-Harper, 1959;.
Opie, E. L.:  Mobilization of Basophile Substance (Ribonucleic Acid) in Cytoplasm of Liver Cells with Production of Tumors by Butter Yellow , J Exp Med 84:91-106 ( (July) ) 1946;.
Anderson, P. J.; Cohen, S.; and Barka, T.:  Hepatic Injury—Histochemical Study of Intracytoplasmic Globules Occurring in Liver Injury , Arch Path 71:89-95 ( (Jan.) ) 1961;.
Weber, G., and Cantero, A.:  Glucose-6-Phosphatase Studies in Normal, Precancerous and Neoplastic Liver , Cancer Res 15:105-108 ( (Feb.) ) 1955;.
Potter, V. R.:  Biochemical Approach to Cancer Problem , Fed Proc 17:691-697 ( (July) ) 1958;.
Miller, E. C., and Miller, J. A.:  Symposium on Immunogenetics and Carcinogenesis; in Vivo Combinations Between Carcinogens and Tissue Constituents and Their Possible Role in Carcinogenesis , Cancer Res 12:547-556 ( (Aug.) ) 1952;.

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Glinos, A. D.; Bucher, N. L. R.; and Aub, J. C.:  Effect of Liver Regeneration on Tumor Formation in Rats Fed 4-Dimethylaminoazobenzene , J Exp Med 93:313-324 ( (April) ) 1951;.
Arcos, J. C.; Griffith, G. W.; and Cunningham, R. W.:  Fine Structural Alterations in Cell Particles During Chemical Carcinogenesis. 2. Further Evidence for Their involvement in Mechanism of Carcinogenesis. Swelling of Rat Liver Mitochondria During Feeding of Amino Azo Dyes . J Biophys Biochem Cytol 7:49-60 ( (Feb.) ) 1960;.
Miller, J. A., and Miller, E. C.:  Carcinogenicity of Certain Derivatives of p-Dimethylaminoazobenzene in Rat , J Exp Med 87:139-156 ( (Feb.) ) 1948;.
Wachstein, M., and Meisel, F.:  On Histochemical Demonstration of Glucose-6-Phosphatase , J Histochem Cytochem 4:592 ( (Nov.) ) 1956;.
Stewart, H. L., and Snell, K. C.:  Histopathology of Experimental Tumors of Liver of Rat , in The Psysiopathology of Cancer (Ed. 2) by Homburger, F.: New York: Hoeber-Harper, 1959;.
Opie, E. L.:  Mobilization of Basophile Substance (Ribonucleic Acid) in Cytoplasm of Liver Cells with Production of Tumors by Butter Yellow , J Exp Med 84:91-106 ( (July) ) 1946;.
Anderson, P. J.; Cohen, S.; and Barka, T.:  Hepatic Injury—Histochemical Study of Intracytoplasmic Globules Occurring in Liver Injury , Arch Path 71:89-95 ( (Jan.) ) 1961;.
Weber, G., and Cantero, A.:  Glucose-6-Phosphatase Studies in Normal, Precancerous and Neoplastic Liver , Cancer Res 15:105-108 ( (Feb.) ) 1955;.
Potter, V. R.:  Biochemical Approach to Cancer Problem , Fed Proc 17:691-697 ( (July) ) 1958;.
Miller, E. C., and Miller, J. A.:  Symposium on Immunogenetics and Carcinogenesis; in Vivo Combinations Between Carcinogens and Tissue Constituents and Their Possible Role in Carcinogenesis , Cancer Res 12:547-556 ( (Aug.) ) 1952;.
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