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Cytotoxicity and DNA damage to mammalian cells by nitrofurans
Abstract:
Nitrofurazone, nitrofurantoin, furazolidone, furaltadone and N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) were toxic to cultured mouse L cells. The extent of toxocity and the rate of reduction of nitrofurazone increased markedly as the oxygen content of the incubation medium was lowered. The toxic effect of nitrofurans was decreased by addition of serum and was much greater in phosphate-buffered saline containing glucose (PSG) than in medium. Damage to L cell DNA by nitrofurans increased as the oxygen concentration decreased from 21% to 0%. The concentration of nitrofurazone and duration of exposure also determined the number of DNA single-strand breaks. It is suggested that toxicity and DNA damage may result from the actions of toxic intermediates in the metabolic reduction of nitrofurans.
Insights
Nitrofurans, including nitrofurazone, are toxic to mouse cells. Lower oxygen levels and specific conditions increase their toxicity and DNA damage potential, possibly due to metabolic reduction intermediates.
Area of Science:
- Toxicology
- Cell Biology
- Molecular Biology
Background:
- Nitrofurans are a class of antimicrobial drugs.
- Their toxicity mechanisms are not fully understood.
- Understanding nitrofurans' effects on mammalian cells is crucial.
Purpose of the Study:
- To investigate the toxicity of various nitrofurans on cultured mouse L cells.
- To determine the influence of oxygen concentration on nitrofurans' toxicity and DNA damaging effects.
- To explore factors affecting nitrofurans' cytotoxicity.
Main Methods:
- Exposure of cultured mouse L cells to nitrofurazone, nitrofurantoin, furazolidone, furaltadone, and FANFT.
- Varying oxygen concentrations in the incubation medium.
- Assessing cell toxicity and DNA single-strand breaks.
- Evaluating the effects of serum and phosphate-buffered saline with glucose (PSG).
Main Results:
- Nitrofurans demonstrated toxicity to mouse L cells.
- Toxicity and nitrofurazone reduction rates increased significantly with decreased oxygen levels.
- DNA damage in L cells escalated as oxygen concentration dropped from 21% to 0%.
- Serum reduced nitrofurans' toxic effects, while PSG enhanced them.
Conclusions:
- Nitrofurans exhibit oxygen-dependent toxicity and genotoxicity in mammalian cells.
- Reduced oxygen enhances nitrofurans' DNA-damaging potential.
- Toxic intermediates from nitrofurans' metabolic reduction are implicated in toxicity and DNA damage.