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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
2000-3-7
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pubmed:abstractText |
Melphalan is a bifunctional alkylating agent that covalently binds with intracellular nucleophilic sites. A methodology using electrospray mass spectrometry was developed to detect and identify DNA adducts. Alkylation sites within a particular nucleotide were examined using electrospray tandem mass spectrometry hyphenated to capillary liquid chromatography in combination with a column switching system. In the reaction mixtures resulting from the interaction of 2'-deoxynucleotides and melphalan several base-aklylated adducts were found. In the case of 2'-deoxyadenosine monophosphate, thymidine monophosphate and 2'-deoxyguanosine phosphate alkylation was observed in the mononucleotide reaction mixtures but not in the DNA-hydrolysates. Calf thymus DNA was reacted in vitro with melphalan. The DNA pellet was isolated and enzymatically hydrolyzed with the aid of Nuclease P1. In this hydrolysate both mono-alkylated 2'-deoxynucleotides and dinucleotides were found. The most important adduct found was identified as the N-7 alklylated dGMP adduct. The alkylated dinucleotides were identified as a pdApdT/melphalan and pdGpdC/melphalan the latter being the most important.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1387-2273
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
736
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
43-59
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10676983-Alkylation,
pubmed-meshheading:10676983-Animals,
pubmed-meshheading:10676983-Cattle,
pubmed-meshheading:10676983-Chromatography, High Pressure Liquid,
pubmed-meshheading:10676983-DNA,
pubmed-meshheading:10676983-DNA Adducts,
pubmed-meshheading:10676983-Deoxyadenine Nucleotides,
pubmed-meshheading:10676983-Deoxycytidine Monophosphate,
pubmed-meshheading:10676983-Deoxyguanine Nucleotides,
pubmed-meshheading:10676983-Deoxyribonucleotides,
pubmed-meshheading:10676983-Mass Spectrometry,
pubmed-meshheading:10676983-Melphalan,
pubmed-meshheading:10676983-Sensitivity and Specificity,
pubmed-meshheading:10676983-Thymidine Monophosphate
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pubmed:year |
1999
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pubmed:articleTitle |
Analysis of melphalan adducts of 2'-deoxynucleotides in calf thymus DNA hydrolysates by capillary high-performance liquid chromatography-electrospray tandem mass spectrometry.
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pubmed:affiliation |
Department of Chemistry, University of Antwerp, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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