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PMID: 8108398 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Free radical adducts induce alterations in DNA cytosine methylation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 4 ·1994-02-15 ·Pages 1261-4

Weitzman SA, Turk PW, Milkowski DH, Kozlowski K

Abstract

Methylation of cytosines in DNA is important for the regulation of expression of many genes. During carcinogenesis, normal patterns of gene methylation can be altered. Oxygen radical injury, shown to damage DNA in a variety of ways associated with cancer development and other conditions, has been suggested to affect DNA methylation, but a mechanism has not been demonstrated. Using oligonucleotides containing the common oxygen radical adduct 8-hydroxyguanine to replace guanine, we found that the enzymatic methylation of adjacent cytosines is profoundly altered. Furthermore, there is a high degree of positional specificity with respect to this effect. Thus, free radical injury may explain some of the altered methylation observed during carcinogenesis.

MeSH Terms
Base Sequence Cytosine/metabolism DNA/metabolism DNA Damage DNA-Cytosine Methylases/drug effects,metabolism Free Radicals Guanine/analogs & derivatives,pharmacology Molecular Sequence Data Oligodeoxyribonucleotides/metabolism,pharmacology Oxygen S-Adenosylmethionine/metabolism Substrate Specificity
Chemicals
Free Radicals Oligodeoxyribonucleotides 8-hydroxyguanine Guanine S-Adenosylmethionine Cytosine DNA DNA modification methylase HpaII DNA-Cytosine Methylases Oxygen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Weitzman S A
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Turk P W
Milkowski D H
Kozlowski K
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34 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.4.1261
Published
1994-02-15
Pages
1261-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43137
Subset
IM
Grants
NIA NIH HHS · R01 AG11536 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.4.1261 PMC Full Text View journal details
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