Document Detail

Mutational spectrum induced in Saccharomyces cerevisiae by the carcinogen N-2-acetylaminofluorene.
MedLine Citation:
PMID:  7845359     Owner:  NLM     Status:  MEDLINE    
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)
A Roy; R P Fuchs
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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    
UPR Cancérogenèse et Mutagenèse Moléculaire et Structurale, IBMC CNRS, Strasbourg, France.
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MeSH Terms
2-Acetylaminofluorene / toxicity*
Base Sequence
DNA Adducts
DNA Mutational Analysis
DNA, Fungal
Molecular Sequence Data
Mutagenicity Tests
Mutagens / toxicity*
Orotidine-5'-Phosphate Decarboxylase / genetics
Saccharomyces cerevisiae / drug effects,  genetics
Transformation, Genetic
Reg. No./Substance:
0/DNA Adducts; 0/DNA, Fungal; 0/Mutagens; 53-96-3/2-Acetylaminofluorene; EC'-Phosphate Decarboxylase

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