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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1981-2-26
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pubmed:abstractText |
The effects of steroid-induced modifications of chromatin structure on the extent and sites of chloroethylnitrosourea binding to chromatin were studied using log-phase HeLa cells. The cells were exposed to 0.1 to 2.0 microM hydrocortisone for 22 hr; this resulted in depressed DNA synthesis while transcriptional activity was stimulated. Hydrocortisone had no effect upon cellular or nuclear uptake of the two nitrosoureas under study, 0.6 mM chlorozotocin or 1-(2-chloroethyl-3-cyclohexyl-1-nitrosourea). Both drugs were found to alkylate transcriptional chromatin preferentially, as demonstrated by DNase II and DNase I digestion. This alkylation was stimulated 2-fold by the same micromolar concentrations of hydrocortisone, 0.1 to 2.0 microM, which stimulated transcription. The extent of nuclear RNA alkylation, determined using RNase T2 as a probe, was found to contribute less than 20% of total chromatin alkylation and was unaffected by steroid pretreatment. Instead, the increased alkylation within these chromatin subfractions was attributed to a steroid-induced alteration of chromatin structure. Electron microscopic examination of HeLa nuclear morphology revealed a hydrocortisone-induced disaggregation of nuclear membrane-associated heterochromatin resulting in a more heterogeneous, less condensed distribution of chromatin. Such data are consistent with a relaxation of the supercoiled chromatin structure, resulting in increased transcription and increased accessibility of potential target sites for nitrosourea alkylation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrocortisone,
http://linkedlifedata.com/resource/pubmed/chemical/Magnesium,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrosourea Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleases
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3697-3703
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7438052-Alkylation,
pubmed-meshheading:7438052-Binding Sites,
pubmed-meshheading:7438052-Cell Nucleus,
pubmed-meshheading:7438052-Chromatin,
pubmed-meshheading:7438052-DNA,
pubmed-meshheading:7438052-Deoxyribonucleases,
pubmed-meshheading:7438052-HeLa Cells,
pubmed-meshheading:7438052-Histocytochemistry,
pubmed-meshheading:7438052-Humans,
pubmed-meshheading:7438052-Hydrocortisone,
pubmed-meshheading:7438052-Magnesium,
pubmed-meshheading:7438052-Nitrosourea Compounds,
pubmed-meshheading:7438052-Ribonucleases
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pubmed:year |
1980
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pubmed:articleTitle |
Influence of hydrocortisone on the binding of nitrosoureas to nuclear chromatin subfractions.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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