Abstract:
:Several genotoxicity endpoints have been evaluated to define nonlinear dose-responses for SN 1 and SN 2 alkylating genotoxicants. Dose-response studies acknowledging the process of multistage tumorigenesis are important; however, data pertaining nonlinearity are not yet available. In this communication, the role of DNA repair in the dose-response relationship for benign papillomas was examined using the two-stage skin carcinogenesis protocol. The data obtained with O(6) -methylguanine-DNA methyltransferase (MGMT) overexpressing mice in which papillomas were induced by a single topical treatment with N-methyl-N-nitrosourea (MNU) followed by promotion with 12-O-tetradecanoylphorbol-13-acetate are reported. As MGMT efficiently protects cells from mutations by repairing O(6) -methylguanine, a miscoding lesion induced by MNU, the question whether MGMT is able to nullify carcinogenic lesions to an extent where they would be considered nonhazardous has been addressed. It is shown here that MGMT overexpression significantly protects against, but does not completely nullify, the effect of MNU in tumor initiation. The possible mechanisms involved have also been discussed.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Becker K,Thomas AD,Kaina Bdoi
10.1002/em.21834subject
Has Abstractpub_date
2014-03-01 00:00:00pages
145-50issue
2eissn
0893-6692issn
1098-2280journal_volume
55pub_type
杂志文章abstract::Fluorescence in situ hybridization with 7, 17, X, and Y chromosome-specific DNA probe was used to investigate the ability of Adriamycin (AM) to induce aneuploidy in interphase human lymphocytes. The reliability of the probes was tested by hybridization to metaphases and interphase nuclei of untreated normal lymphocyte...
journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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doi:10.1002/em.22377
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21988
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1077
更新日期:2001-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21696
更新日期:2012-06-01 00:00:00