Linked Life Data

2654627

Source:http://linkedlifedata.com/resource/pubmed/id/2654627

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1989-6-14
pubmed:abstractText
To determine whether it is possible to separate antitumour and mutagenic properties in the nitracrine series, a number of 4-substituted derivatives of the hypoxia-selective drug nitracrine have been evaluated for their mutagenic effects at three loci in several strains of Salmonella typhimurium differing in DNA-repair capacity (uvrB, recA, plasmid pKM101). The drugs divided into two series in terms of their biological effects. Group A compounds (nitracrine and its Cl, F, Me and OMe derivatives) were very toxic to bacteria, and uvrB and recA deletions enhanced toxicity by 10-80-fold. Mutagenic potency was high, being slightly enhanced by uvrB and reduced by recA deletions. In contrast the toxicities and mutagenic potentials of Group B compounds (COOMe, NMe2, and two other bulky amine derivatives) were reduced by at least an order of magnitude, with uvrB and recA deletions showing lesser influence. The COOMe derivative was the only compound showing greater effects at the hisC3076 locus than the hisD3052 or hisG46 loci. The data suggest that all the compounds cause mutations through intercalation and/or monoadduct formation, but only for the COOMe derivative is intercalation the dominant mode of action. Group A compounds appear to have the additional ability to cross-link DNA, a property which amounts for their high potency but which is not compatible with bulky 4-substituents. Apart from these generalizations, there was considerable variation in mutagenic efficiency (as measured by the maximum numbers of revertant colonies) within each series. Of the compounds studied, the 4-OMe derivative appears to best retain the desirable antitumour properties of nitracrine while showing greatly-reduced mutagenic potential, and is an interesting lead for further development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
223
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13-22
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Mutagenic activity of nitracrine derivatives in Salmonella typhimurium: relationship to drug physicochemical parameters, and to bacterial uvrB and recA genes and plasmid pKM101.
pubmed:affiliation
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't