Carcinogenesis, Vol 19, 305-310, Copyright © 1998 by Oxford University Press
TH Broschard, A Lebrun-Garcia and RP Fuchs
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a strong mutagen/carcinogen,
belongs to a group of heterocyclic amines that are formed (ng/g amounts)
during the cooking of protein containing food. The mutational specificity
of IQ in Escherichia coli was determined in a forward mutation assay using
the yeast URA3 gene as a target. The plasmid pTU-AC, containing the target
URA3, was randomly modified in vitro using N-hydroxy-IQ, and subsequently
transformed into an E. coli pyrF strain (DB6656). Mutant clones were
directly selected by their ability to grow on medium containing
5-fluoro-orotic acid which is toxic to URA3+ clones and thereby selects for
URA3- mutants. Single Strand Conformation Polymorphism (SSCP) was used to
map the mutation- containing regions of URA3, so that it was necessary to
sequence only the relevant, mutation-containing fragment and not the entire
gene. At a modification level of 7 IQ-lesions/URA3 gene, the predominant
mutations were base substitutions (approximately 70%), followed by complex
gene rearrangements (approximately 20%) and frameshifts (approximately
10%). More than 96% of the base substitutions occurred at G:C base pairs
and were predominantly G:C-->A:T transitions, followed by G:C-->T:A
and G:C-->C:G transversions. Next neighbour analysis revealed that
deoxyguanosines situated within the sequence 5'- TGC were more susceptible
to mutations induced by IQ. With one exception, all frameshift mutations
were -1 deletions at runs of three consecutive dGs. At higher
IQ-modification levels, predominantly complex sequence rearrangements were
observed.
ARTICLES
Mutagenic specificity of the food mutagen 2-amino-3-methylimidazo[4,5- f]quinoline in Escherichia coli using the yeast URA3 gene as a target
Unite de Cancerogenese et Mutagenese Moleculaire et Structuale/CNRS UPR 9003, Pole API, Ecole Superieure de Biotechnologie de Strasbourg, Illkirch-Graffenstaden, France.
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