Genotoxic evaluation of norfloxacin and pipemidic acid with the Escherichia coli Pol A-/Pol A+ and the ames test.
BACKGROUND
Genotoxicity of antibiotics has not been well evaluated, and there is not much information on the genetic risk of quinolone drugs, even though they are widely used as alternative choice drugs in urinary infections.


METHODS
Pipemidic acid and norfloxacin were tested for their capacity to induce point mutations using the Ames test and DNA damage on Escherichia coli PolA-/PolA+.


RESULTS
At non-toxic doses, all of the drugs studied were negative on the E. coli PolA-/PolA+ test with or without in vitro metabolic activation with induced arochlor 1254 rat liver (S9). They did not produce frameshift mutations in TA98, or base-pair substitutions in S. typhimurium hisG46 strains TA100, or UTH8414. Norfloxacin and its induced metabolites in vitro with S9 rat liver were mutagenic to hisG48 strains TA102 and TA104, both of which detect oxidative chemicals. Pipemidic acid induced mutations in S. typhimurium hisG48 strains only when they had an efficient DNA excision repair system.


CONCLUSIONS
These results suggest that the risk of oxygen-free radical generation from quinolones should be considered.
Hospital Juárez de México, Dirección de Investigación y Enseñanza, México, D.F.
M
M
Arriaga-Alba
F
F
Barrón-Moreno
R
R
Flores-Paz
E
E
García-Jiménez
R
R
Rivera-Sánchez
D000818:Animals; D004249:DNA Damage; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D016368:Frameshift Mutation / Q000187:drug effects; D009152:Mutagenicity Tests; D009643:Norfloxacin / Q000633:toxicity*; D010876:Pipemidic Acid / Q000633:toxicity*; D017354:Point Mutation / Q000187:drug effects; D011061:Poly A; D051381:Rats; D012486:Salmonella typhimurium
D011061:Poly A; D010876:Pipemidic Acid; D009643:Norfloxacin