Structural basis of the mutagenicity of heterocyclic amines formed during the cooking processes.
A data base consisting of 61 heterocyclic amines formed during food preparation and their des-amino analogs were subjected to structure-activity analysis using the CASE method, a structural activity relational expert system. The program identified the major structural determinants associated with mutagenic activity or lack thereof. The structures identified as contributing to the probability of activity as well as those associated with mutagenic potency were highly predictive of molecules not in the learning set. The major structural determinant, the aromatic amino moiety, and quantum mechanical calculations revealed that the mutagenic potency associated with this functionality derived from their contribution to the energy of the Lowest Unoccupied Molecular Orbital (LUMO).
Zhang
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Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261.
Klopman
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Rosenkranz
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D000588:Amines / Q000737:chemistry / Q000633:toxicity*; D016009:Chi-Square Distribution; D003296:Cooking; D004789:Enzyme Activation; D005103:Expert Systems; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000633:toxicity*; D015394:Molecular Structure; D015999:Multivariate Analysis; D016296:Mutagenesis; D009153:Mutagens / Q000737:chemistry*; D011789:Quantum Theory; D012044:Regression Analysis; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D013499:Surface Properties
D000588:Amines; D006571:Heterocyclic Compounds; D009153:Mutagens