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• W2153551504 endingPage "1494" @default.
• W2153551504 startingPage "1487" @default.
• W2153551504 abstract "DNA methylation at the 5-position on the cytosine ring in CpG dinucleotides (CpG sites) appears to play an important role in regulating gene expression. In general, there is an inverse relationship between promoter CpG site methylation and the potential for transcription. Thus, changes in DNA methylation density may lead to altered levels of proteins such as glutathione S-transferase pi (GSTP), which is frequently used as a marker to detect hepatocellular foci and neoplasms in the rat. In the present study, the level of CpG methylation in the rat GSTP promoter region was determined in bisulfite-treated DNA isolated from control (untreated) rat livers, chemically induced, GSTP-positive rat liver neoplasms, and methyl-deficient rat livers that contained numerous GSTP-positive foci after administration of a defined diet deficient in folate and choline and low in methionine (0.18%). Eight cytosines between -235 and + 140 in the GSTP promoter region were methylated in a site-specific manner in GSTP-negative control liver, whereas these same sites were hypomethylated in all four chemically-induced, GSTP-positive neoplasms. Similarly, all CpG sites were unmethylated in methyl-deficient liver DNA within 3 weeks of the rats receiving the methyl-deficient diet, and they remained unmethylated throughout the 36-week treatment period. Five of the eight CpG sites are located within consensus sequences for the DNA binding proteins Spl and E2F. This indicates at least one possible mechanism that could potentially lead to transcriptional activation of GSTP in hepatocellular foci and neoplasms during rat hepatocarcinogenesis. These findings suggest that methylation of critical cytosines within the promoter region rather than all CpG-associated cytosines may be a determining factor in regulation of GSTP expression." @default.
• W2153551504 created "2016-06-24" @default.
• W2153551504 creator A5017792432 @default.
• W2153551504 creator A5021876882 @default.
• W2153551504 creator A5037379883 @default.
• W2153551504 creator A5062637673 @default.
• W2153551504 date "1998-08-01" @default.
• W2153551504 modified "2023-09-26" @default.
• W2153551504 title "Hypomethylation of the rat glutathione S-transferase pi (GSTP) promoter region isolated from methyl-deficient livers and GSTP-positive liver neoplasms" @default.
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• W2153551504 doi "https://doi.org/10.1093/carcin/19.8.1487" @default.
• W2153551504 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9744547" @default.
• W2153551504 hasPublicationYear "1998" @default.
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