Document Detail


Mutational spectrum induced in Saccharomyces cerevisiae by the carcinogen N-2-acetylaminofluorene.
MedLine Citation:
PMID:  7845359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The spectrum of mutations induced by the carcinogen N-2-acetylaminofluorene (AAF) was analysed in Saccharomyces cerevisiae using a forward mutation assay, namely the inactivation of the URA3 gene. The URA3 gene, carried on a yeast/bacterial shuttle vector, was randomly modified in vitro using N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF) as a model reactive metabolite of the carcinogen AAF. The binding spectrum of AAF to the URA3 gene was determined and found to be essentially random, as all guanine residues reacted about equally well with N-AcO-AAF. Independent Ura- mutants were selected in vivo after transformation of the modified plasmid into a ura3 delta yeast strain. Plasmid survival decreased as a function of AAF modification, leading to one lethal hit (37% relative survival) for an average of approximately 50 AAF adducts per plasmid molecule. At this level of modification the mutation frequency was equal to approximately 70 x 10(-4), i.e. approximately 50-fold above the background mutation frequency. UV irradiation of the yeast cells did not further stimulate the mutagenic response, indicating the lack of an SOS-like mutagenic response in yeast. Sequence analysis of the URA3 mutants revealed approximately 48% frameshifts, approximately 44% base substitutions and approximately 8% complex events. While most base substitutions (74%) were found to be targeted at G residues where AAF is known to form covalent C8 adducts, frameshift mutations were observed at GC base pairs in only approximately 24% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
A Roy; R P Fuchs
Related Documents :
15611159 - Spontaneous mutations in diploid saccharomyces cerevisiae: more beneficial than expected.
20206679 - The protein kinase hal5p is the high-copy suppressor of lithium-sensitive mutations of ...
9054459 - Critical role of the second stirrup region of the tata-binding protein for transcriptio...
9230069 - Plasma membrane translocation of fluorescent-labeled phosphatidylethanolamine is contro...
1423589 - Pcf4 encodes an rna polymerase iii transcription factor with homology to tfiib.
20300059 - Genetic studies of human dna repair proteins using yeast as a model system.
17464359 - Gemini pollen 2, a male and female gametophytic cytokinesis defective mutation.
15611159 - Spontaneous mutations in diploid saccharomyces cerevisiae: more beneficial than expected.
24077769 - The evolution of small insertions and deletions in the coding genes of drosophila melan...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular & general genetics : MGG     Volume:  245     ISSN:  0026-8925     ISO Abbreviation:  Mol. Gen. Genet.     Publication Date:  1994 Oct 
Date Detail:
Created Date:  1995-03-09     Completed Date:  1995-03-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0125036     Medline TA:  Mol Gen Genet     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  69-77     Citation Subset:  IM    
Affiliation:
UPR Cancérogenèse et Mutagenèse Moléculaire et Structurale, IBMC CNRS, Strasbourg, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
2-Acetylaminofluorene / toxicity*
Base Sequence
DNA Adducts
DNA Mutational Analysis
DNA, Fungal
Molecular Sequence Data
Mutagenicity Tests
Mutagens / toxicity*
Orotidine-5'-Phosphate Decarboxylase / genetics
Plasmids
Saccharomyces cerevisiae / drug effects,  genetics
Transformation, Genetic
Chemical
Reg. No./Substance:
0/DNA Adducts; 0/DNA, Fungal; 0/Mutagens; 53-96-3/2-Acetylaminofluorene; EC 4.1.1.23/Orotidine-5'-Phosphate Decarboxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A mating-type factors of Coprinus cinereus have variable numbers of specificity genes encoding two c...
Next Document:  Sequencing of genes within the vir regulon of Streptococcus pyogenes type M15--an opacity factor-pos...