The relationship between 8-oxo-7,8-dihydro-2'-deoxyguanosine level and extent of cytosine methylation in leukocytes DNA of healthy subjects and in patients with colon adenomas and carcinomas.

2.50
Hdl Handle:
http://hdl.handle.net/10146/36592
Title:
The relationship between 8-oxo-7,8-dihydro-2'-deoxyguanosine level and extent of cytosine methylation in leukocytes DNA of healthy subjects and in patients with colon adenomas and carcinomas.
Authors:
Guz, Jolanta; Foksinski, Marek; Siomek, Agnieszka; Gackowski, Daniel; Rozalski, Rafal; Dziaman, Tomasz; Szpila, Anna; Olinski, Ryszard
Abstract:
It has been known for a long time that DNA hypomethylation occurs in many human cancers and precancerous conditions. However, the mechanisms of hypomethylation are largely unknown. It is possible that endogenous 8-oxo-7,8-dihydroguanine (8-oxoGua) level may be linked to aberrant DNA methylation of adjacent cytosine and in this way influences carcinogenesis. Therefore, the aim of the present study was to assess a possible link between 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) background level and 5-methylcytosine content in DNA from human leukocytes of healthy subjects (n=105) as well as in patients with colon adenomas (n=39) and carcinomas (n=50). Our results demonstrated statistically significant negative correlation between background level of 8-oxodG and 5-methylcytosine content in DNA isolated from leukocytes of healthy donors (r=-0.3436, p=0.0003). The mean content of 5-methylcytosine was significantly lower, while 8-oxodG level was significantly higher in leukocytes DNA of patients with colon adenomas and carcinomas in comparison with healthy subjects. The mean values for 5-methylcytosine were: 3.59+/-0.173% (healthy subjects), 3.38+/-0.128% (patients with adenomas), 3.40+/-0.208% (colon cancer patients). The mean values of 8-oxodG in DNA were, respectively: 4.67+/-1.276, 5.72+/-1.787, 5.76+/-1.884 8-oxodG per 10(6) dG molecules. DNA from affected tissue (colon) suffered from significant, about 10% reduction in cytosine methylation in comparison with leukocytes of the paired subjects. Our work provides the first in vivo evidence suggesting that increased levels of 8-oxodG in DNA may lead to carcinogenesis not only via mispair/mutagenic potential of the modified base but also through its ability to influence gene expression by affecting DNA methylation.
Citation:
Mutat. Res. 2008, 640 (1-2):170-173
Journal:
Mutation Research
Issue Date:
2-Apr-2008
URI:
http://hdl.handle.net/10146/36592
DOI:
10.1016/j.mrfmmm.2007.12.013
PubMed ID:
18281064
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2C-4RJ9X8C-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=1843694&md5=76487200caba885b4f8110ed6f8c9792
Type:
Article
Language:
en
ISSN:
0027-5107
Sponsors:
The authors of this paper are partners of ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:“Food Quality and Safety” (Contract No. 513943). R.O. was supported by a Foundation for Polish Science fellowship.
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Full metadata record

DC FieldValue Language
dc.contributor.authorGuz, Jolanta-
dc.contributor.authorFoksinski, Marek-
dc.contributor.authorSiomek, Agnieszka-
dc.contributor.authorGackowski, Daniel-
dc.contributor.authorRozalski, Rafal-
dc.contributor.authorDziaman, Tomasz-
dc.contributor.authorSzpila, Anna-
dc.contributor.authorOlinski, Ryszard-
dc.date.accessioned2008-08-27T11:47:55Z-
dc.date.available2008-08-27T11:47:55Z-
dc.date.issued2008-04-02-
dc.identifier.citationMutat. Res. 2008, 640 (1-2):170-173en
dc.identifier.issn0027-5107-
dc.identifier.pmid18281064-
dc.identifier.doi10.1016/j.mrfmmm.2007.12.013-
dc.identifier.urihttp://hdl.handle.net/10146/36592-
dc.description.abstractIt has been known for a long time that DNA hypomethylation occurs in many human cancers and precancerous conditions. However, the mechanisms of hypomethylation are largely unknown. It is possible that endogenous 8-oxo-7,8-dihydroguanine (8-oxoGua) level may be linked to aberrant DNA methylation of adjacent cytosine and in this way influences carcinogenesis. Therefore, the aim of the present study was to assess a possible link between 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) background level and 5-methylcytosine content in DNA from human leukocytes of healthy subjects (n=105) as well as in patients with colon adenomas (n=39) and carcinomas (n=50). Our results demonstrated statistically significant negative correlation between background level of 8-oxodG and 5-methylcytosine content in DNA isolated from leukocytes of healthy donors (r=-0.3436, p=0.0003). The mean content of 5-methylcytosine was significantly lower, while 8-oxodG level was significantly higher in leukocytes DNA of patients with colon adenomas and carcinomas in comparison with healthy subjects. The mean values for 5-methylcytosine were: 3.59+/-0.173% (healthy subjects), 3.38+/-0.128% (patients with adenomas), 3.40+/-0.208% (colon cancer patients). The mean values of 8-oxodG in DNA were, respectively: 4.67+/-1.276, 5.72+/-1.787, 5.76+/-1.884 8-oxodG per 10(6) dG molecules. DNA from affected tissue (colon) suffered from significant, about 10% reduction in cytosine methylation in comparison with leukocytes of the paired subjects. Our work provides the first in vivo evidence suggesting that increased levels of 8-oxodG in DNA may lead to carcinogenesis not only via mispair/mutagenic potential of the modified base but also through its ability to influence gene expression by affecting DNA methylation.en
dc.description.sponsorshipThe authors of this paper are partners of ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:“Food Quality and Safety” (Contract No. 513943). R.O. was supported by a Foundation for Polish Science fellowship.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2C-4RJ9X8C-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=1843694&md5=76487200caba885b4f8110ed6f8c9792en
dc.subject5-Methylcytosineen
dc.subject8-oxodGen
dc.subject8-oxo-7,8-dihydro-2′-deoxyguanosineen
dc.subjectHealthy subjecten
dc.subjectColon adenoma and carcinoma patientsen
dc.subject.mesh5-Methylcytosine-
dc.subject.meshAdenoma-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshCarcinoma-
dc.subject.meshColonic Neoplasms-
dc.subject.meshCytosine-
dc.subject.meshDNA Damage-
dc.subject.meshDeoxyguanosine-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLeukocytes-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.titleThe relationship between 8-oxo-7,8-dihydro-2'-deoxyguanosine level and extent of cytosine methylation in leukocytes DNA of healthy subjects and in patients with colon adenomas and carcinomas.en
dc.typeArticleen
dc.identifier.journalMutation Researchen

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