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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
18
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pubmed:dateCreated |
1993-10-1
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pubmed:abstractText |
Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclophosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand beaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks, DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase II Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
|
pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
53
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
4251-6
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8395979-Animals,
pubmed-meshheading:8395979-Apoptosis,
pubmed-meshheading:8395979-DNA Damage,
pubmed-meshheading:8395979-DNA Repair,
pubmed-meshheading:8395979-Etoposide,
pubmed-meshheading:8395979-Mice,
pubmed-meshheading:8395979-NAD,
pubmed-meshheading:8395979-Proto-Oncogene Proteins,
pubmed-meshheading:8395979-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:8395979-Topoisomerase II Inhibitors,
pubmed-meshheading:8395979-Tumor Cells, Cultured
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pubmed:year |
1993
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pubmed:articleTitle |
bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair.
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pubmed:affiliation |
Department of Pathology, Georgetown University School of Medicine, Washington, D.C. 20007.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|