Mutagenic potency of food-derived heterocyclic amines

James S. Felton, Mark G. Knize, Rebekah W. Wu, Michael E. Colvin, Frederick T. Hatch, Michael A. Malfatti

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The understanding of mutagenic potency has been primarily approached using "quantitative structure-activity relationships" (QSAR). Often this method allows the prediction of mutagenic potency of the compound based on its structure. But it does not give the underlying reason why the mutagenic activities differ. We have taken a set of heterocyclic amine structures and used molecular dynamic calculations to dock these molecules into the active site of a computational model of the cytochrome P4501A2 enzyme. The calculated binding strength using Boltzman distribution constants was then compared to the QSAR value (HF/6-31G* optimized structures) and the Ames/Salmonella mutagenic potency. Further understanding will only come from knowing the complete set of mutagenic determinants. These include the nitrenium ion half-life, DNA adduct half-life, efficiency of repair of the adduct, and ultimately fixation of the mutation through cellular processes. For two isomers, PhIP and 3-Me-PhIP, we showed that for the 100-fold difference in the mutagenic potency a 5-fold difference can be accounted for by differences in the P450 oxidation. The other factor of 20 is not clearly understood but is downstream from the oxidation step. The application of QSAR (chemical characteristics) to biological principles related to mutagenesis is explored in this report.

Original languageEnglish (US)
Pages (from-to)90-94
Number of pages5
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume616
Issue number1-2
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Quantitative Structure-Activity Relationship
Amines
Food
Half-Life
DNA Adducts
Molecular Dynamics Simulation
Cytochromes
Salmonella
Mutagenesis
Catalytic Domain
Ions
Mutation
Enzymes
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine

Keywords

  • Heterocyclic amines
  • Mutagenic potency
  • QSAR

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Felton, J. S., Knize, M. G., Wu, R. W., Colvin, M. E., Hatch, F. T., & Malfatti, M. A. (2007). Mutagenic potency of food-derived heterocyclic amines. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 616(1-2), 90-94. https://doi.org/10.1016/j.mrfmmm.2006.11.010

Mutagenic potency of food-derived heterocyclic amines. / Felton, James S.; Knize, Mark G.; Wu, Rebekah W.; Colvin, Michael E.; Hatch, Frederick T.; Malfatti, Michael A.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 616, No. 1-2, 01.03.2007, p. 90-94.

Research output: Contribution to journalArticle

Felton, James S. ; Knize, Mark G. ; Wu, Rebekah W. ; Colvin, Michael E. ; Hatch, Frederick T. ; Malfatti, Michael A. / Mutagenic potency of food-derived heterocyclic amines. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2007 ; Vol. 616, No. 1-2. pp. 90-94.
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