Arriaga-Alba M, Barrón-Moreno F, Flores-Paz R, García-Jiménez E, Rivera-Sánchez R
Hospital Juárez de México, Dirección de Investigación y Enseñanza, México, D.F.
Arch Med Res. 1998 Autumn;29(3):235-40.
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.
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+.
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.
These results suggest that the risk of oxygen-free radical generation from quinolones should be considered.
抗生素的遗传毒性尚未得到充分评估，尽管喹诺酮类药物作为泌尿系统感染的替代选择药物被广泛使用，但关于其遗传风险的信息并不多。
使用艾姆斯试验检测吡哌酸和诺氟沙星诱导点突变的能力，并检测其对大肠杆菌PolA-/PolA+的DNA损伤。
在无毒剂量下，所有研究的药物在有无用诱导型1254多氯联苯大鼠肝脏（S9）进行体外代谢活化的情况下，对大肠杆菌PolA-/PolA+试验均呈阴性。它们在TA98中未产生移码突变，在鼠伤寒沙门氏菌hisG46菌株TA100或UTH8414中未产生碱基对替换。诺氟沙星及其与S9大鼠肝脏体外诱导的代谢产物对hisG48菌株TA102和TA104具有致突变性，这两种菌株均可检测氧化性化学物质。吡哌酸仅在鼠伤寒沙门氏菌hisG48菌株具有有效的DNA切除修复系统时才诱导突变。
这些结果表明应考虑喹诺酮类药物产生氧自由基的风险。
