Hypermethylation of replicating hepatic DNA following N-methyl-N-nitrosourea administration.
Changes in the degree of methylation of cytosine in DNA are considered to be mechanistically important in modulating gene expression. To gain a better understanding of the relationship(s) linking onco-proliferative processes and enzymatic DNA methylation, a study has been carried out on the hepatic DNA methylation pattern during DNA replication following partial hepatectomy (PH), mitogen treatment and N-methyl-N-nitrosourea (MNU) administration in rats. The following results were obtained: (i) DNA hypomethylation was seen during DNA synthesis, with each of the 3 stimuli, namely MNU administration, partial hepatectomy, and hepatomitogen treatment; (ii) the level of DNA hypomethylation was not quantificatively related to the extent of DNA replication as measured by incorporation of [3H]thymidine into hepatic DNA; (iii) MNU administration under conditions conducive to carcinogenic development, i.e. during the S phase of compensatory cell proliferation, caused hypermethylation of replicating hepatic DNA, as shown by HpaII and MspI restriction patterns.
Kanduc
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Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Bari, Italy.
Aresta
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A
Farber
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E
D000818:Animals; D004247:DNA / Q000187:drug effects* / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects*; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008745:Methylation / Q000187:drug effects; D008770:Methylnitrosourea / Q000633:toxicity*; D008934:Mitogens / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D014316:Tritium
D008934:Mitogens; D014316:Tritium; D008770:Methylnitrosourea; D004247:DNA; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific