Linked Life Data

8466904

Source:http://linkedlifedata.com/resource/pubmed/id/8466904

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1993-5-13
pubmed:abstractText
Bistranded DNA damage produced by the enediyne antitumor antibiotic calicheamicin (CAL) was examined in plasmid DNA and in a model site for CAL-mediated DNA damage containing the sequence AGGA.TCCT. CAL was observed to produce bistranded DNA damage to the virtual exclusion of single-strand (SS) lesions. Without expression of drug-induced abasic sites as strand breaks, CAL activated by 10 mM glutathione produced equal numbers of DS and SS breaks in plasmid DNA. However, cleavage of drug-induced abasic sites with hydrazine and putrescine resulted in a dramatic increase in the appearance of bistranded damage, with ratios of DS to SS breaks of approximately 6:1 and approximately 24:1, respectively. A similar bias for DS lesions was noted in CAL-mediated damage in the AGGA.TCCT model sequence, in which evidence for a 4'-hydroxylated abasic site was observed on the AGGA strand. These model DNA systems revealed three important features of the bistranded damage produced by CAL. First, the major lesion produced by CAL is a bistranded lesion consisting of an abasic site on one strand and a direct strand break on the other. Second, 3'-phosphoglycolate residues resulting from CAL-induced C4'-hydrogen abstraction at the C of AGGATC were restricted to bistranded lesions. This unusual behavior of the C4'-chemistry of both CAL and the related neocarzinostatin (NCS) is consistent with an intermediate in the partitioning that is dependent on bistranded lesions. Finally, 4-hydroxythiophenol activated CAL to produce a ratio of DS to SS lesions of approximately 10:1, as opposed to the approximately 1:30 ratio noted previously for NCS.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3617-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Exclusive production of bistranded DNA damage by calicheamicin.
pubmed:affiliation
Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't