Abstract:
:In this study we evaluated the antigenotoxic and cytoprotective capabilities of WR-2721 [S-2-(3-aminopropylamino)-ethylphosphorothioic acid (amifostine)] in different normal tissues of BALB/c mice treated with idarubicin [4-demethoxydaunorubicin (IDA)]. The aminothiol WR-2721 is a pro-drug that requires dephosphorylation to its active metabolite WR-1065, to produce selectively cytoprotective activity in normal tissues exposed to radio- and chemotherapeutic agents, without protecting malignant tissues. IDA is an effective chemotherapeutic agent against hematological diseases, but produces a broad spectrum of toxicity in nontumoral cells. Animals were injected intravenously with WR-2721 (250 mg/kg) or IDA (6 mg/kg) and WR-2721/IDA. Micronuclei frequency in bone marrow was measured 24 and 48 hr after initiation of the treatments. The IDA-treated group showed increased levels of micronuclei. However, the WR-2721- and WR-2721/IDA-treated groups did not show differences from the controls. Genetic damage was evaluated by alkaline single-cell gel electrophoresis at 24-hr posttreatments. Important DNA damage was observed in liver, spleen, and peripheral blood cells of mice treated with IDA. The presence of WR-2721 diminished that damaging effect only in liver cells. The apoptotic index was measured in liver and spleen tissues by the TUNEL assay 14 and 24 hr after treatment. In liver we observed an increased percentage of apoptotic cells at 24 hr for the IDA-treated group, whereas the WR-2721 and WR-2721/IDA groups remained at low levels. Splenic cells treated with IDA and WR-2721/IDA showed increased DNA fragmentation levels at any time. In conclusion, WR-2721 has a tissue-specific antigenotoxic and cytoprotective effect in IDA-treated mice using these experimental conditions.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
de Campos Nebel M,Larripa I,González-Cid Mdoi
10.1002/em.1081subject
Has Abstractpub_date
2002-01-01 00:00:00pages
3-9issue
1eissn
0893-6692issn
1098-2280pii
10.1002/em.1081journal_volume
39pub_type
杂志文章abstract::Lack of cell surface glycosylphosphatidylinositol (GPI)-anchored protein(s) has been used as a reporter of Pig-a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the c...
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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更新日期:2005-01-01 00:00:00
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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.21795
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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.10210
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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更新日期:2004-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
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更新日期:2017-07-01 00:00:00