Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1987-6-25
pubmed:abstractText
The interaction of the nitroimidazole-aziridines RSU-1069 and RSU-1131, as parent or radiation-reduced species, with plasmid DNA in aqueous solution at pH 7 results in strand breakage. The yields of DNA single strand breaks (ssb), "alkali-labile" damage and DNA crosslinks induced by these alkylating agents have been assessed. It is shown that DNA crosslinks are induced only by the reduced nitro-compounds. RSU-1069, as parent or reduced compound, is more efficient at producing these effects than the equivalent form of RSU-1131. Further, RSU-1069 is about 2 X more susceptible to nucleophilic attack by inorganic phosphate and deoxynucleotides than RSU-1131. RSU-1069 also shows greater selectivity for reaction with the nucleotide base moiety than does the less-reactive monomethyl analogue, RSU-1131. The yields of ssb and "alkali-labile" damaged sites induced by the two agents reflect their respective chemical reactivities and appear largely to determine their aerobic cytotoxicities. In contrast, the yield of DNA crosslinks induced by the reduced compounds appears to correspond rather better with the observed hypoxic cytotoxicities. From these findings it is suggested that the induction of DNA crosslinks by these agents may play a major role in their effectiveness as hypoxia-selective cytotoxins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1787-92
pubmed:dateRevised
2006-5-1
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Induction of DNA crosslinks in vitro upon reduction of the nitroimidazole-aziridines RSU-1069 and RSU-1131.
pubmed:publicationType
Journal Article