Linked Life Data

7523879

Source:http://linkedlifedata.com/resource/pubmed/id/7523879

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-10-31
pubmed:abstractText
The mutagenicity of the antitumor agent ICR-170 (2-methoxy-6-chloro-9-[(ethyl-2-chloroethyl)amino propylamino] acridine dihydrochloride) in the adenine-3 (ad-3) region was studied with a two-component heterokaryon (H-12) of Neurospora crassa. The objective was to characterize the genetic damage produced by this acridine nitrogen mustard derivative to determine in a lower eukaryotic organism the basis for its potent activity against ascites tumors in mice. As in higher eukaryotes, specific-locus mutations in the ad-3 region of strain H-12 result from gene/point mutations, multiple-locus mutations, and multilocus deletion mutations at the closely linked ad-3A and ad-3B loci. Six different treatments of conidial suspensions of H-12 with ICR-170 were used to obtain dose-response curves for inactivation of conidia as well as the overall induction of ad-3 forward mutations using a direct method based on pigment accumulation rather than a requirement for adenine. These experiments demonstrated that: (1) the slope of the dose-response curve for ICR-170-induced specific-locus mutations in the ad-3 region was 1.97 +/- 0.02, and (2) ICR-170 is a potent mutagen (maximum forward-mutation frequency between 1000 and 10,000 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Both biochemical and classical genetic tests were used to characterize the ICR-170-induced ad-3 mutations from each of the six treatments to distinguish the different genotypic classes and subclasses. The overall data base demonstrates that ICR-170-induced ad-3 mutations result exclusively from gene/point mutations at the ad-3A and ad-3B loci and not multilocus deletion mutations. In addition, the frequency of multiple-locus ad-3 mutations resulting from gene/point mutations at the ad-3A and ad-3B loci with a separate site of recessive lethal damage elsewhere in the genome increases as a function of dose. However, an exceptionally high frequency of multiple-locus ad-3 mutations consisting of gene/point mutations at the ad-3A and ad-3B loci with a separate site of closely linked recessive lethal damage was found at all doses. Comparison of the dose-response curves for the major classes and subclasses of ICR-170-induced ad-3 mutations demonstrates that the gene/point ad-3 mutations and multiple-locus ad-3 mutations with a separate site of recessive lethal damage elsewhere in the genome have different induction kinetics.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
310
pubmed:geneSymbol
ad-3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Forward-mutation tests on the antitumor agent ICR-170 in Neurospora crassa demonstrate that it induces gene/point mutations in the ad-3 region and an exceptionally high frequency of multiple-locus ad-3 mutations with closely linked sites of recessive lethal damage.
pubmed:affiliation
Center for Life Sciences and Toxicology, Research Triangle Institute, Research Triangle Park, NC 27709-2194.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.