Mutagenicity of N2 guanylarylation is SOS functions dependent and reminiscent of the high mutagenic property of 4NQO.
A comparison of the mutagenic potency of the N2 and the C8 guanylarylation of DNA by 4-nitroquinoline 1-oxide (4NQO) was established. The induced mutagenicity by the N2 guanine adduct is dependent on the SOS functions in the host and requires the umuC gene product. This lesion is repaired by the excision repair system and efficiently blocks the replication machinery. The data obtained with the C8 adduct show that this lesion is weakly toxic in the wild-type strain Escherichia coli probably because the efficiency of the replication is affected. This adduct is three times less mutagenic than the N2 adduct. These results suggest that in vivo the high mutagenicity of 4NQO can mainly be ascribed to the N2 guanine adduct.
Galiègue-Zouitina
S
S
Unité 124 INSERM, Institut de Recherches sur le Cancer de Lille, France.
Daubersies
P
P
Loucheux-Lefebvre
M H
MH
Bailleul
B
B
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006147:Guanine; D007700:Kinetics; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009600:Nitroquinolines / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects; D013014:SOS Response, Genetics; D013604:T-Phages / Q000201:enzymology
D009153:Mutagens; D009600:Nitroquinolines; D015112:4-Nitroquinoline-1-oxide; D006147:Guanine; D004247:DNA; D004259:DNA-Directed DNA Polymerase