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Hypermethylation of replicating hepatic DNA following N‐methyl‐N‐nitrosourea administration
Author(s) -
Kanduc Darja,
Aresta Antonella,
Farber Emmanuel
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580322
Subject(s) - dna methylation , dna , dna replication , methylation , microbiology and biotechnology , biology , dna synthesis , carcinogen , thymidine , cytosine , gene , cancer research , biochemistry , gene expression
Abstract 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 [ 3 H]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 Hpall and Mspl restriction patterns.