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Mutagenicity of organophosphorus compounds in bacteria and Drosophila
Abstract:
140 Organophosphorus compounds (OP's) have been tested for mutagenic activity in bacteria, principally by using two specially constructed sets of tester strains of the bacteria Salmonella typhimurium and Escherichia coli. It was found that 20% gave positive mutagenic responses and that this group of chemicals produce base subsitutions rather than frame-shift mutations. In most cases the DNA repair genes exrA+ and recA+ were required for mutagenic activity. Seven compounds were further tested in Drosophila melanogaster for the ability to induce recessive lethal mutations. In some of these cases the doses administered to the flies had to be very low due to the highly toxic nature of the compounds. To over-come this problem, the accumulation of recessive lethal mutations was measured in populations which were continually exposed to the compounds over a period of some 18 months. During this time the populations developed increased resistance to the compound and so the dose administered could gradually be increased. Six of the compounds were mutagenic. Of the compounds tested in both systems, those showing mutagenic activity in bacteria were also mutagenic in Drosophila, those not mutagenic in bacteria were not mutagenic in Drosophila.
Insights
Organophosphorus compounds (OPs) were tested for mutagenicity. Most mutagens caused base substitutions, requiring DNA repair genes, and were confirmed in Drosophila melanogaster, indicating broad genotoxicity.
Area of Science:
- Toxicology
- Genetics
- Microbiology
Background:
- Organophosphorus compounds (OPs) are widely used but their mutagenic potential requires thorough investigation.
- Bacterial mutagenicity assays are crucial for initial screening of chemical genotoxicity.
Purpose of the Study:
- To evaluate the mutagenic activity of 140 organophosphorus compounds using bacterial assays.
- To assess the genotoxic potential of selected OPs in a higher organism, Drosophila melanogaster.
- To correlate mutagenic responses between bacterial and Drosophila models.
Main Methods:
- Mutagenicity testing of 140 OPs using Salmonella typhimurium and Escherichia coli tester strains.
- Investigation of DNA repair gene involvement (exrA+, recA+) in bacterial mutagenicity.
- Recessive lethal mutation assays in Drosophila melanogaster populations chronically exposed to OPs.
Main Results:
- 20% of tested OPs exhibited mutagenic activity in bacteria, primarily inducing base substitutions.
- DNA repair genes exrA+ and recA+ were necessary for the mutagenic activity of most bacterial mutagens.
- Six of seven OPs tested in Drosophila melanogaster induced recessive lethal mutations.
- A strong correlation was observed: OPs mutagenic in bacteria were also mutagenic in Drosophila.
Conclusions:
- Organophosphorus compounds represent a significant genotoxic risk, with a notable percentage showing mutagenic potential.
- Bacterial mutagenicity assays effectively predict genotoxicity in Drosophila, validating their use in risk assessment.
- The mechanism of OP-induced mutagenesis in bacteria involves base substitutions and requires DNA repair pathways.