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

It is generally accepted that the DNA methylation pattern in a particular cell type is stable over the cell generations and is clonally inherited by a semiconservative mechanism in which the methylation of the progeny strand is determined by the 5-methylcytosine residue present in the parental strand. In our experiments, we have been able to show that the chemical carcinogens MNU, MNNG, and L-ethionine affect the methylation process either by modification of the DNA substrate or by interference at the cofactor level. The changes introduced into the cellular methylation pattern persist and are inherited in the progeny cells regardless of whether the carcinogens or their adducts in the DNA persist in the cell or not. The carcinogen-induced hypomethylation correlates with the increased transcriptional complexity of the nRNA of treated cells, indicating the initiation of transcription at sites previously inactive. This means that chemical carcinogens can cause, by interference with the process of DNA methylation, stable changes in the program of genetic expression; the possibility that such changes are related to the process of initiation of carcinogenesis should not be overlooked.
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PMID:Alteration of enzymatic DNA methylation by chemical carcinogens. 630 48

DNA-RNA hybridization studies, using nuclear RNA's (nRNA's) labeled in vivo and in vitro with high specific radioactivities, were performed to compare the nRNA populations of normal rat liver, livers treated with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), and 3'-Me-DAB-induced hepatomas. The study with normal liver nRNA labeled by i.p. injection of [3H]orotic acid indicated that the nuclei of a 3'-Me-DAB-induced transplanted hepatoma, AH136B, lacked some RNA species present in normal liver nuclei. No qualitative difference in thee RNA populations was seen between normal liver and the livers of rats fed a carcinogenic amount of 3'-Me-DAB, either alone or in combination with 4-nitrostilbene which enhanced the azo dye carcinogenesis. Then, nRNA's of both normal liver and AH136B hepatoma were labeled in vitro by phosphorylation with polynucleotide kinase and adenosine 5'-[gamma-32P]triphosphate. The competitive hybridization with 32P-labeled normal liver nRNA was competed, and the deletion of RNA in the nuclei of AH136B hepatoma or 3'-Me-DAB-induced primary hepatoma was estimated to be 15% or more in the measure of radioactivity of the hybridized normal liver nRNA. 32P-labeled AH136B hepatoma nRNA was completed completely by liver nRNA's, suggesting that no unique RNA species were present in the hepatoma nuclei.
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PMID:Analysis of loss of nuclear RNA in azo dye-induced hepatoma by DNA-RNA competitive hybridization. 705 6