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Abstract:
Using the Ames plate reversion and fluctuation tests, the mutagenic activity of chloroquine was tested in the new tester strains of Salmonella typhimurium, TA97, TA102, and Escherichia coli strains WP2, WP2hcr, WP6 and WP67. The E. coli transconjugants obtained from the mating transfer of R-plasmid(s) in strains TA97 and TA102 respectively to E. coli WP2, i.e. EE97 and EE102, were also tested. Chloroquine reverted strain TA97 from histidine dependence to independence and also reverted E. coli strains EE97 and EE102 from tryptophan dependence to independence. The E. coli strains WP2, WP2hcr; WP6 and WP67 and S. typhimurium TA102 were not affected. S. typhimurium TA97 could be reverted with 250 ng/ml of chloroquine (therapeutic blood level of chloroquine is 300 ng/ml). Reversion generally occurred optimally at the relatively lower concentrations of chloroquine i.e. 25, 50 micrograms/ml than at higher concentrations. From the properties of the reverted tester strains, the results indicated that chloroquine per se mediated frameshift reversion.
Insights
Chloroquine demonstrates mutagenic activity, specifically causing frameshift reversion in Salmonella typhimurium TA97 and Escherichia coli EE97/EE102 strains. This mutagenicity was observed at concentrations near therapeutic blood levels.
Area of Science:
- Microbiology
- Genetics
- Toxicology
Background:
- Chloroquine is an antimalarial drug with potential genotoxic effects.
- Assessing drug mutagenicity is crucial for understanding safety profiles.
Purpose of the Study:
- To evaluate the mutagenic potential of chloroquine.
- To identify specific mechanisms of chloroquine-induced mutations.
Main Methods:
- Utilized Ames plate reversion and fluctuation tests.
- Employed Salmonella typhimurium (TA97, TA102) and Escherichia coli (WP2, WP2hcr, WP6, WP67) tester strains.
- Tested E. coli transconjugants (EE97, EE102) harboring R-plasmids.
Main Results:
- Chloroquine induced frameshift reversion in Salmonella typhimurium TA97.
- Chloroquine also reverted Escherichia coli strains EE97 and EE102.
- Mutagenic effects were observed at therapeutic blood levels (250 ng/ml) and optimally at lower concentrations (25-50 µg/ml).
- No mutagenic effects were observed in E. coli WP2, WP2hcr, WP6, WP67, or S. typhimurium TA102.
Conclusions:
- Chloroquine exhibits mutagenic activity, primarily through a frameshift reversion mechanism.
- The study highlights the genotoxic potential of chloroquine, particularly at clinically relevant concentrations.