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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1993-1-11
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pubmed:abstractText |
Human lymphoblastoid cell lines derived from WI-L2 exhibit unexpected frequencies of diaminopurine (DAP) resistant mutants. The background mutant fractions of 10(-7) to 10(-8) in untreated cultures are much lower than the frequencies expected for loss of a heterozygous autosomal locus (10(-5) to 10(-6), yet much higher than expected for a homozygous locus (10(-10) to 10(-12). We used aminopterin, adenine and thymidine (AAT) to select DAP-sensitive (DAPS) revertants from one resistant line. The background frequency of DAPR in these revertant cell lines ranged from 3.5 to 6.5 x 10(-4), approximately the square root of 10(-7). Thus these data suggest that both alleles of aprt are inactivated at similarly high frequencies. They also indicate that the DAPS revertants were heterozygotes (aprt +/-) or hemizygotes (aprt +/0) and that WI-L2 was homozygous (aprt+/+). Mutational dose-response studies with X-rays, ethyl methanesulfonate (EMS), and ICR-191 were conducted in 4 of these revertant cell lines. EMS and ICR-191, which induce mainly point mutations, did not induce an increase in mutant fraction. A dose of 200 cGy X-rays, however, induced a frequency of 10(-3). Treatment of DAPR cells with 5-azacytidine induced a significant increase in reversion to DAPS. Southern blot analysis of the aprt gene after digestion with MspI or HpaII also suggests that differential methylation changes may play a major role in the generation of DAP sensitivity and resistance.
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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/2,6-diaminopurine,
http://linkedlifedata.com/resource/pubmed/chemical/2-Aminopurine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenine Phosphoribosyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Aminacrine,
http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Ethyl Methanesulfonate,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrogen Mustard Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/acridine half-mustard
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-5107
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
284
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pubmed:geneSymbol |
aprt
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
287-95
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1281280-2-Aminopurine,
pubmed-meshheading:1281280-Adenine Phosphoribosyltransferase,
pubmed-meshheading:1281280-Aminacrine,
pubmed-meshheading:1281280-Azacitidine,
pubmed-meshheading:1281280-Blotting, Southern,
pubmed-meshheading:1281280-Cell Line,
pubmed-meshheading:1281280-DNA,
pubmed-meshheading:1281280-Dose-Response Relationship, Drug,
pubmed-meshheading:1281280-Dose-Response Relationship, Radiation,
pubmed-meshheading:1281280-Drug Resistance,
pubmed-meshheading:1281280-Ethyl Methanesulfonate,
pubmed-meshheading:1281280-Gene Frequency,
pubmed-meshheading:1281280-Humans,
pubmed-meshheading:1281280-Mutagens,
pubmed-meshheading:1281280-Mutation,
pubmed-meshheading:1281280-Nitrogen Mustard Compounds,
pubmed-meshheading:1281280-X-Rays
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pubmed:year |
1992
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pubmed:articleTitle |
Heritable alterations at the adenine phosphoribosyltransferase (APRT) locus in human lymphoblastoid cell lines.
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pubmed:affiliation |
Laboratory of Radiobiology, Harvard School of Public Health, Boston, MA 02115.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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