Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the carcinogen 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB) on the gene expression of rat liver was studied. Hybridization analysis with enriched neoplastic liver specific cDNA demonstrated a noticeable change in gene expression during liver carcinogenesis. The effect of 3'-MDAB on liver specific gene expression was also studied with albumin and alpha-fetoprotein (AFP) genes as models. Serum AFP levels increased dramatically during hepatocarcinogenesis. Amounts of AFP mRNA present in polysomal poly(A)mRNA were determined by translation and hybridization experiments. AFP mRNA increased in carcinogen-treated liver as the serum level of AFP increased. Increase of AFP mRNA in liver cytoplasmic RNAs can be detected as early as 18 days after feeding rats 3'-MDAB and reached peaks at 30-40 and 185 days of treatment. AFP serum level and AFP mRNA in liver cytosol decreased dramatically between these peaks, with a small amount of AFP mRNA and serum AFP detectable in rats treated with 3'-MDAB for 100 days. The increase in amount of AFP mRNA was due to an increase in transcription of the AFP gene in livers of rats treated with carcinogen. Only a slight change in serum albumin concentration and albumin mRNA in livers of rats treated with 3'-MDAB was noticed.
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PMID:The alteration of gene expression in rat liver during chemical carcinogenesis. 683 26

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.
Carcinogenesis 1996 Jun
PMID:Different patterns of expression of ornithine decarboxylase mRNAs in rat liver after acute administration of hepatocarcinogens. 868 50

The introduction includes a literature review of DNA reactive species and DNA adduct formation that results from aromatic amine N-oxidation catalyzed by hepatic cytochrome P450 vs. that catalyzed by nonhepatic peroxidases. Experimental evidence is then described for a novel oxidative stress mechanism involving prooxidant N-cation radical formation by both oxidases, which is proposed as a contributing mechanism for aromatic amine induced cytotoxicity and carcinogenesis. Aromatic amine N-cation radicals formed by peroxidases were found to cooxidize GSH or NADH and form reactive oxygen species. The latter could explain the reported DNA oxidative damage found in vivo following methylaminoazobenzene administration [Hirano et al. Analyses of Oxidative DNA Damage and Its Repair Activity in the Livers of 3'-Methyl-4-dimethylaminoazobenzene-Treated Rodents. Jpn. J. Cancer Res. 2000, 91, 681-685]. It was also found that the prooxidant activity of the aromatic amine increased as its redox potential, i.e., ease of oxidation decreased with o-anisidine and aminofluorene being the most effective at forming reactive oxygen species. This suggests that the rate-limiting step in the cooxidation is the rate of arylamine oxidation by the peroxidase. Incubation of hepatocytes with aromatic amines caused a decrease in the mitochondrial membrane potential before cytotoxicity ensued. The CYP1A2-induced hepatocytes isolated from 3-methylcholanthrene administered rats were much more susceptible to some arylamines and were protected by CYP1A2 inhibitors. Hepatocyte GSH was also depleted by all arylamines tested and extensive GSH oxidation occurred with o-anisidine and aminofluorene, which was prevented by CYP1A2 inhibitors. This suggests that in intact hepatocytes CYP1A2 may also catalyze a one-electron oxidation of some arylamines to form prooxidant cation radicals, which cooxidize GSH to form the reactive oxygen species.
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PMID:N-oxidation of aromatic amines by intracellular oxidases. 1221 66