Linked Life Data

8062258

Source:http://linkedlifedata.com/resource/pubmed/id/8062258

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1994-9-20
pubmed:abstractText
The methylating agent N-methylnitrosourea (MNU) is biased, surprisingly, in its carcinogenic potential toward the mouse thymus. Previous studies have shown that single doses of MNU administered to adult mice induced thymic lymphomas in over 80% of mice, while transgenic mice expressing high levels of the human O6-alkylguanine-DNA alkyltransferase gene in the thymus (MGMT-CD2 transgenics) were protected from developing MNU-induced lymphomas. The mechanism of this protection was examined in this report. In nontransgenic mice given a lymphomagenic dose of 80 mg/kg MNU, depletion of thymic alkyltransferase activity occurred within 3 h and remained undetectable for the subsequent 192 h; whereas in MGMT-CD2-transgenic mice, this dose of MNU did not deplete thymic alkyltransferase, and the lowest level of alkyltransferase was still 10-fold higher than the constitutive level of thymic alkyltransferase in nontransgenic mice. Likewise, the level of O6-methylguanine adducts detected in the thymus of nontransgenic mice was 96 pg/micrograms guanine 3 h after MNU compared to only 8 pg/micrograms guanine in transgenic mice. By 18 h, the level of O6-methylguanine in MGMT-CD2-transgenic mice was below 2 pg/micrograms guanine, compared to over 70 pg/micrograms guanine in nontransgenic mice. In contrast, no differences were noted in the liver between groups because the MGMT transgene is not expressed in the liver of this strain of mouse. Our data establish that rapid O6-methylguanine-DNA adduct repair due to enhanced levels of alkyltransferase in MGMT-CD2-transgenic mice blocks the initiation of MNU-induced carcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4648-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Rapid repair of O6-methylguanine-DNA adducts protects transgenic mice from N-methylnitrosourea-induced thymic lymphomas.
pubmed:affiliation
Cancer Center, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4937.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't