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Naturally occurring carbonyl compounds are mutagens in Salmonella tester strain TA104
Abstract:
Strains of Salmonella typhimurium that carry a nonsense mutation at the site of reversion detect a variety of naturally occurring and synthetic carbonyl compounds as direct-acting mutagens. TA104 is reverted efficiently by formaldehyde, alpha, beta-unsaturated aldehydes (enals), and dicarbonyl compounds, such as diacetyl and glutaraldehyde. This strain is much more sensitive to carbonyl mutagenesis than is TA100, a strain previously reported to detect aldehydes as mutagens, or any other characterized strains of Salmonella. Long-chain enals are very toxic to TA104, but addition of a reduced glutathione chase following an incubation period decreases this toxicity, thus enabling the detection of 4-hydroxy-pentenal, a homolog of the lipid peroxidation product, 4-hydroxy-nonenal, as a mutagen. This is the first report of the mutagenicity of a hydroxy-enal, a class of enals produced by lipid peroxidation. Testing conducted with strains that carry the nonsense mutation in different repair backgrounds indicates that the presence of pKM101 and the deletion of the uvrB gene facilitate the detection of enals and dicarbonyls, but not malondialdehyde, as mutagens. Since carbonyl compounds are widely distributed in foods, are generated during cellular metabolism, and are present in body fluids, they may make a significant contribution to the risk of human cancer.
Insights
A new Salmonella typhimurium strain, TA104, efficiently detects carbonyl compounds like aldehydes and dicarbonyls as mutagens. This discovery is crucial for understanding cancer risks from widespread carbonyls in food and metabolism.
Area of Science:
- Genetics and Microbiology
- Toxicology and Carcinogenesis
Background:
- Carbonyl compounds are ubiquitous in food, metabolism, and bodily fluids.
- Certain carbonyls are known mutagens, posing potential cancer risks.
- Existing Salmonella strains have limitations in detecting a wide range of carbonyl mutagens.
Purpose of the Study:
- To characterize the mutagenicity of various carbonyl compounds using a novel Salmonella typhimurium strain.
- To investigate the role of specific genetic backgrounds in carbonyl mutagen detection.
- To assess the potential contribution of carbonyls to human cancer risk.
Main Methods:
- Utilized Salmonella typhimurium strain TA104, possessing a specific nonsense mutation for mutagen detection.
- Tested a variety of naturally occurring and synthetic carbonyl compounds, including aldehydes (enals) and dicarbonyls.
- Employed a reduced glutathione chase to mitigate toxicity of long-chain enals, enabling detection of hydroxy-enals.
- Assessed mutagenicity in strains with different repair backgrounds (pKM101 presence, uvrB deletion).
Main Results:
- Salmonella typhimurium TA104 demonstrated high sensitivity to carbonyl mutagenesis, detecting formaldehyde, enals, and dicarbonyls.
- TA104 is more sensitive to carbonyl mutagenesis than previously characterized Salmonella strains like TA100.
- The mutagenicity of 4-hydroxy-pentenal, a lipid peroxidation product, was reported for the first time.
- The pKM101 plasmid and uvrB deletion enhanced detection of enals and dicarbonyls, but not malondialdehyde.
Conclusions:
- Salmonella typhimurium TA104 is a sensitive tool for detecting a broad spectrum of carbonyl mutagens.
- Hydroxy-enals represent a newly identified class of mutagens produced by lipid peroxidation.
- Carbonyl compounds may significantly contribute to human cancer risk due to their widespread presence and mutagenicity.