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Heterocyclic amine mutagenicity/carcinogenicity: influence of repair, metabolism, and structure
1Biology and Biotechnology Program, Lawrence Livermore National Laboratory CA 94550, USA.
Abstract:
Cooking, heat processing, and pyrolysis of protein-rich foods induce the formation of structurally related heterocyclic aromatic amines that have been found to be mutagenic in bacteria, mammalian cells in culture and mice. All these compounds are potent mutagens and most are active below 1 ng/plate, in Ames/Salmonella tester strain TA1538 in the presence of S9 liver microsomal preparations from rat, mouse, or hamster. They are also potent in strains TA98, TA97, moderately active in TA1537, weakly active in TA100, and virtually inactive in TA1535 and TA102. Thus, they show powerful frameshift activity in reverting specific GC-rich sequences, but do not cause base substitution mutations or revert an AT-rich sequence. They are 100-fold less active in the uvrB+, repair-proficient strain TA1978, and in the case of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ), cause insertions and large deletions not seen in TA1538.
Insights
Cooking protein-rich foods creates mutagenic heterocyclic aromatic amines (HAAs). These potent mutagens cause frameshift mutations in bacterial assays, highlighting their genotoxic potential.
Area of Science:
- Food Science
- Toxicology
- Genetics
Background:
- Cooking and heat processing of protein-rich foods generate heterocyclic aromatic amines (HAAs).
- These HAAs are structurally related and have demonstrated mutagenicity across various biological systems, including bacteria, cultured mammalian cells, and mice.
- Previous research has identified HAAs as potent mutagens, necessitating further investigation into their specific mechanisms of action.
Purpose of the Study:
- To characterize the mutagenic activity of heterocyclic aromatic amines (HAAs) formed during food processing.
- To determine the specific types of mutations induced by HAAs in bacterial test systems.
- To investigate the influence of DNA repair proficiency on HAA-induced mutagenesis.
Main Methods:
- Utilized Ames/Salmonella assays with various tester strains (TA1538, TA98, TA97, TA1537, TA100, TA102) to assess mutagenicity.
- Employed S9 liver microsomal preparations from rat, mouse, and hamster to mimic mammalian metabolic activation.
- Compared mutagenic activity in repair-proficient (uvrB+) and repair-deficient bacterial strains to evaluate DNA repair mechanisms.
Main Results:
- Heterocyclic aromatic amines (HAAs) exhibited potent mutagenicity, with significant activity observed at concentrations below 1 ng/plate in Ames strain TA1538 with S9 activation.
- HAAs demonstrated strong frameshift mutagenic activity, primarily targeting GC-rich sequences, and were less effective in inducing base substitution mutations.
- Mutagenic potency varied across different Salmonella strains, with highest activity in TA98 and TA97, moderate in TA1537, weak in TA100, and negligible in TA1535 and TA102.
- A 100-fold reduction in activity was noted in the repair-proficient strain TA1978 compared to repair-deficient strains.
- Specific HAA, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), induced insertions and large deletions in the repair-proficient strain, a phenomenon not observed in TA1538.
Conclusions:
- Heterocyclic aromatic amines (HAAs) are potent frameshift mutagens generated during food processing.
- Their mutagenic activity is dependent on the bacterial strain and DNA repair capacity.
- The observed mutagenic mechanisms, including frameshift mutations and insertions/deletions, underscore the genotoxic risks associated with HAA exposure from cooked foods.