5-Methylcytosine in CpG sites and the reactivity of nearest neighboring guanines toward the carcinogen aflatoxin B1-8,9-epoxide.
Autor: | Ross MK; Department of Community and Environmental Medicine, University of California, Irvine, Irvine, California, 92697-1825, USA., Mathison BH, Said B, Shank RC |
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Jazyk: | angličtina |
Zdroj: | Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1999 Jan 08; Vol. 254 (1), pp. 114-9. |
DOI: | 10.1006/bbrc.1998.9895 |
Abstrakt: | The reactivity of guanines in an oligonucleotide containing mutational hot spots within the p53 gene (codons 248 and 249), 5'-CCG1G2AG3G4CCCA-3', toward dimethyl sulfate (DMS) and aflatoxin B1-8,9-epoxide (AFB1-8,9-epoxide) was investigated by a modified Maxam-Gilbert technique. 5-Methylcytosine in the CpG site of codon 248 did not appear to modulate the reactivity of target guanines G1, G2, G3, and G4 toward either genotoxin when compared to the sequence containing a nonmethylated CpG site. A similar experiment was conducted in which a 0.5-kb fragment of the human HPRT gene containing exon 1 and several CpG sites was treated with UV-activated aflatoxin B1. Results showed that guanine adduct formation was independent of the methylation status of the CpG site. These findings are discussed in relation to other studies that have shown that cytosine methylation has an inhibiting effect, an enhancing effect, or no effect on adduct formation with nearby guanine nucleotides. (Copyright 1999 Academic Press.) |
Databáze: | MEDLINE |
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