Different patterns of expression of ornithine decarboxylase mRNAs in rat liver after acute administration of hepatocarcinogens.
(57/58)
In the present study, we have evaluated the induction of ornithine decarboxylase (ODC) activity in rat liver after acute in vivo administration of different hepatocarcinogens, and correlated the ODC activity peaks with the accumulation of the three ODC-related mRNA species in rat liver at different times after the intraperitoneal injection of different hepatocarcinogens. ODC activity peaked 16 h after 2-acetylaminofluorene (2-AAF) treatment, while accumulation of the three ODC-mRNAs, starting 4 h after the injection, was maximal 6 h later. Thioacetamide (TAA) administration caused a single peak of ODC activity 20 h after treatment, while there had been the maximum increases of the three ODC-mRNAs 4-h earlier. The first ODC activity peak occurred 20 h after treatment with 3'-methyl-4-(dimethylamino)azobenzene (MDAB), at the same time that accumulation of the ODC-mRNAs was maximum. There was no increase in ODC-mRNA accumulation at 28 h or 36 h after MDAB treatment, the time at which ODC activity once again peaked. All the ODC-related transcripts accumulated after MDAB treatment, although to different degrees. The 1.7 kilobase (kb) transcript accumulated the most after 2-AAF treatment. After TAA treatment, the 2.2 kb mRNA was the most abundantly expressed. In neonatal liver, in which ODC activity is physiologically high, the 1.7 kb mRNA is expressed more abundantly than the other two ODC-related transcripts. These results demonstrate that the peak of ODC enzyme activity does not always correspond in time with the peak of ODC-mRNA accumulation; that different hepatocarcinogens induce different patterns of accumulation of the ODC-related transcripts; and that the minor ODC-related transcript (1.7 kb) in rat liver seems to be expressed not only constitutively but is also inducible. (+info)
Newer insights into the pathogenesis of liver cancer.
(58/58)
A new hypothesis leading to a new model of liver carcinogenesis is described; it is based on the acquisition by carcinogen-altered hepatocytes during initiation of a new functional handle--resistance to the cytotoxicity of a carcinogen--and on the ability of such cells to proliferate in an environment that prevents proliferation of normal hepatocytes. The creation of such a differential environment now enables a quantitative analysis for initiation, the beginning synchronization of the putative premalignant hepatocytes for about 15 cell cycles, the study of the pattern of growth of such resistant cells to form nodules that have some resemblance to the organizational pattern of fetal liver, the analysis of the appearance of distinctive positive and negative markers for these cells, and the further investigation of the development of liver cancer from such cells. The remarkable similarity in overall pattern betweeen the development of cancer in the skin and in the liver with chemicals and the possible role of both somatic mutation and neodifferentiation in carcinogenesis are briefly discussed. (+info)