Linked Life Data

6430903

Source:http://linkedlifedata.com/resource/pubmed/id/6430903

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1984-9-17
pubmed:abstractText
Covalent adducts formed from the ultimate carcinogen 7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[ a]pyrene inhibit the enzyme-catalyzed transfer of methyl groups from S-adenosylmethionine to cytosine residues in DNA. Two DNA methyltransferase enzymes, isolated from the bacterium Haemophilus and mouse spleen nuclei, were tested for their ability to methylate carcinogen-modified substrates in vitro. These model enzymes possess the known methylation activities found in mammalian cells, de novo, and maintenance methylation of CpG-containing nucleotide sequences. The in vitro alkylation of DNA substrates by the carcinogen effectively decreases the methyltransferase reaction of both enzymes in a manner that is directly dependent upon the level of covalent modification of the DNA. Inhibition of de novo methylation activity can be detected at very low levels of carcinogen modification, 1 hydrocarbon residue per 20,000-40,000 nucleotides. Adduct levels in this range are capable of initiating transformation. Both enzymes are inactivated by direct reaction with the carcinogen in the absence of DNA. We also find that carcinogen adducts are capable of inhibiting DNA methylation at CpG sites removed from the primary lesion. These results support the proposal that carcinogen-induced DNA damage can cause alterations in methylation patterns that may eventually lead to heritable changes in gene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
259
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9711-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Inhibition of DNA methyltransferases in vitro by benzo[a]pyrene diol epoxide-modified substrates.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't