Initiation of Experimental Liver Carcinogenesis by Chemicals: Are the Carcinogen Altered Hepatocytes Stimulated to Grow into Foci by Different Selection Procedures Identical?
The multi-stage nature of the carcinogenic process has been demonstrated in many tissues including skin (1–3), liver (4, 5), mammary gland (6), urinary bladder (7) and vagina (8). However, the molecular mechanisms underlying this complex process are not yet understood clearly. The development of several experimental model systems for the sequential analysis of chemical carcinogenesis in rat liver has opened up new avenues for investigating this complex process. Our experimental approaches have two main objectives (i) to understand the mechanisms underlying the initiation phase of liver carcinogenesis and (ii) to characterize the initiated hepatocytes stimulated to grow into enzyme altered foci by some of the selection procedures. The experimental design was guided by the hypothesis shown in Figure 1.
KeywordsSelection Regimen Orotic Acid Chemical Carcinogenesis Positive Focus Liver Carcinogenesis
Unable to display preview. Download preview PDF.
- 3.T.J. Slaga, A. Sivak, and R. K. Boutwell, eds., Carcinogenesis. Vol. 2. Mechanisms of Tumour Promotion and Cocarcinogenesis. Raven Press, New York (1978).Google Scholar
- 7.R.M. Hics, and J. Chowaniec, Experimental induction, histology and ultrastructure of hyperplasia and neoplasia of the urinary bladder epithelium. Int. Rev. Exp. Pathol. 18: 199 (1968).Google Scholar
- 16.T.S. Ying, The role of DNA synthesis and of repair in the induc- tion of putative preneoplastic lesions in rat liver by 1, 2-dimethylhydrazine (1, 2-DMH). Proc.Am.Assoc.Cancer Res. 21: 62 (1980).Google Scholar
- 20.S.E. Abanobi, A. Columbano, R.A. Mulivor, S. Rajalakshmi, and D.S.R. Sarma, In vivo replication of hepatic deoxyribonucleic acid of rats treatededwithi d imethyl nitrosam ine: presence of dimethylnitrosamine-induced 06-methylguanine, N-7-methylguanine, and N-3-methyladenine in the replicated hybrid deoxyribonucleic acid. Biochemistry 19: 1382 (1980).PubMedCrossRefGoogle Scholar
- 21.G.M. Ledda, A. Columbano, P.M. Rao, S. Rajalakshmi, and D.S.R. Sarma, In vivo replication of carcinogen-modified rat liver DNA: Increased susceptibility of 06-methylguanine compared to N-7-methylguanine in replicated DNA to S1-nuclease. Biochem. Biophys. Res. Commun. 95: 816 (1980).PubMedCrossRefGoogle Scholar