Mutation spectra of the two guanine adducts of the carcinogen 4-nitroquinoline 1-oxide in Escherichia coli. Influence of neighbouring base sequence on mutagenesis.
When the chemical carcinogen 4-nitroquinoline 1-oxide binds to DNA in vitro, two major adducts are formed, both at guanine residues, but at different positions, i.e. the C8 or the N2 position. Well-defined adducts (either C8 or N2 guanine adducts) can be formed in vitro by reacting DNA with 4-actoxyaminoquinoline 1-oxide (Ac-4HAQO) under different reaction conditions. Forward mutations induced by each of both main 4NQO adducts in the tetracycline resistance gene of pBR322 were determined. In total, 30 independent 4NQO-induced mutations were characterized, showing mainly base-pair substitution mutations and some frameshift mutations. We have observed that the 5' neighbouring base influences the specificity of dGuo-N2-AQO induced base-pair substitutions mutagenesis; a similar effect does not occur with dGuo-C8-AQO. This study reveals the importance of the N2 guanine adduct in the mutagenesis induced by 4NQO in vivo.
Daubersies
P
P
Unité 124 INSERM, Institut de Recherches sur le Cancer de Lille, France.
Galiègue-Zouitina
S
S
Koffel-Schwartz
N
N
Fuchs
R P
RP
Loucheux-Lefebvre
M H
MH
Bailleul
B
B
D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism*; D000595:Amino Acid Sequence; D000634:Aminoquinolines / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests
D000634:Aminoquinolines; D015112:4-Nitroquinoline-1-oxide; C032983:N-(deoxyguanosin-C(8)-yl)-4-aminoquinoline 1-oxide; D004247:DNA; C073579:3-(deoxyguanosin-N2-yl)-4-aminoquinoline 1-oxide; D003849:Deoxyguanosine