Abstract
Cytoplasmic changes were investigated in livers of rats at various intervals up to 50 weeks during primary induction of hepatoma by thioacetamide feeding.
Microsomal Glucose-6-phosphatase and ATPase activities were shown to decrease progressively with increased period of thioacetamide feeding the fall in activities being more pronounced during the first 15 weeks.
Hormonal induction of tryptophan pyrrolase and tyrosine transaminase activities was shown to undergo a significant decrease of 65% and 55% respectively at the end of 50 weeks feeding.
The substrate induced tryptophan pyrrolase activity was decreased to 50% during the 50 weeks period whereas the substrate induced tyrosine transaminase activity gradually increased to 200%. The latter is attributable to differences in the optimal induction dose of tyrosine in normal and carcinogen fed rats.
The m-RNA template lifetime for tryptophan pyrrolase was shown to be exceeding 24 hours in normal rats as against that of 13 hours in rats fed with carcinogen for 30 weeks. On the other hand the m-RNA template lifetime for tyrosine transaminase was 3 hours in control rats while it was 7 hours in the carcinogen fed rats.
The observed changes were shown to occur long before the onset of malignant transformation.
The alterations in terms of decreased Glucose-6-phosphatase and substrate induced tryptophan pyrrolase activities were shown to be reversible when the carcinogen was withdrawn from the diet after 30 weeks of feeding.
The significance of these observations is discussed in relation to damage to endoplasmic reticulum during hepatocarcinogenesis.
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Selected References
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- AUERBACH V. H., WAISMAN H. A. Amino acid metabolism of Novikoff hepatoma. Cancer Res. 1958 Jun;18(5):543–547. [PubMed] [Google Scholar]
- CHAN S. K., McCOY T. A., KIZER D. E. The deletion of tryptophan peroxidase activity during dye carcinogenesis. Cancer Res. 1960 Oct;20:1303–1308. [PubMed] [Google Scholar]
- Fitzhugh O. G., Nelson A. A. Liver Tumors in Rats Fed Thiourea or Thioacetamide. Science. 1948 Dec 3;108(2814):626–628. doi: 10.1126/science.108.2814.626. [DOI] [PubMed] [Google Scholar]
- ICHII S. Studies on tryptophan peroxidase in the liver of tumor-bearing animals. Gan. 1958 Jun;49(2):125–136. [PubMed] [Google Scholar]
- Imai K., Omura T., Sato R. Biochemical characterization of microsomes isolated from heart and skeletal muscles. J Biochem. 1966 Sep;60(3):274–285. doi: 10.1093/oxfordjournals.jbchem.a128434. [DOI] [PubMed] [Google Scholar]
- KNOX W. E. The adaptive control of tryptophan and tyrosine metabolism in animals. Trans N Y Acad Sci. 1963 Mar;25:503–512. doi: 10.1111/j.2164-0947.1963.tb01471.x. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- PITOT H. C., PERAINO C., BOTTOMLEY R. H., MORRIS H. P. The comparative enzymology and cell origin of rat hepatomas. III. Some enzymes of amino acid metabolism. Cancer Res. 1963 Jan;23:135–142. [PubMed] [Google Scholar]
- Papaconstantinou J. Molecular aspects of lens cell differentiation. Science. 1967 Apr 21;156(3773):338–346. doi: 10.1126/science.156.3773.338. [DOI] [PubMed] [Google Scholar]
- ROSEN F., HARDING H. R., MILHOLLAND R. J., NICHOL C. A. GLUCOCORTICOIDS AND TRANSAMINASE ACTIVITY. VI. COMPARISON OF THE ADAPTIVE INCREASES OF ALANINE- AND TYROSINE-ALPHA-KETOGLUTARATE TRANSAMINASES. J Biol Chem. 1963 Nov;238:3725–3729. [PubMed] [Google Scholar]
- ROSEN F., MIHICH E., NICHOL C. A. SELECTIVE METABOLIC AND CHEMOTHERAPEUTIC EFFECTS OF VITAMIN B6 ANTIMETABOLITES. Vitam Horm. 1964;22:609–641. doi: 10.1016/s0083-6729(08)60355-6. [DOI] [PubMed] [Google Scholar]
- VILLALOBOS J. G., Jr, STEELE W. J., BUSCH H. EFFECTS OF THIOACETAMIDE ON LABELING OF RIBONUCLEIC ACID OF ISOLATED NUCLEOLI IN VITRO. Biochim Biophys Acta. 1964 Oct 16;91:233–238. doi: 10.1016/0926-6550(64)90246-4. [DOI] [PubMed] [Google Scholar]
- WEBER G. BEHAVIOR AND REGULATION OF ENZYME SYSTEMS IN NORMAL LIVER AND IN HEPATOMAS OF DIFFERENT GROWTH RATES. Adv Enzyme Regul. 1963;1:321–340. doi: 10.1016/0065-2571(63)90028-1. [DOI] [PubMed] [Google Scholar]
- WEBER G., MORRIS H. P. COMPARATIVE BIOCHEMISTRY OF HEPATOMAS. III. CARBOHYDRATE ENZYMES IN LIVER TUMORS OF DIFFERENT GROWTH RATES. Cancer Res. 1963 Aug;23:987–994. [PubMed] [Google Scholar]
