Table 1. Some of the required interdisciplinary research, analytic methods, and tools needed to understand the possible connection of mutagens in cooked food to cancer.

Issues
  • What cooked foods contain mutagens?
  • What are the
    mutagenic compounds?
  • What amounts are produced?




  • By what mechanism are mutagens formed during cooking?





  • How potent (mutagenic) are the compounds?






  • How are mutagens activated metabolically?






  • How is DNA affected?











  • How are tumors induced?




  • What are the health
    risks from exposure?
  • What people are
    affected?
  • Who is most at risk?




  • Research required
  • Chemical extraction
    and purification
  • Identification and quantification
  • Proof of structure
  • Synthesis of isomers




  • Study precursors and reaction conditions in chemical models
  • Aqueous vs dry heating
  • Vary cooking temperature


  • Mutagenicity research (e.g., use chemical to innduce mutations,
    and count frequency
    of mutant cells or chromosomal changes)


  • Study chemical intermediates (bioactivation pathways)
  • Modulate metabolism in cell models
  • Radioactive labeling


  • DNA damage
    and repair
  • DNA binding analysis
  • DNA adduct analysis








  • Carcinogenicity research (e.g., assess tumor induction in various tissues in laboratory animals)

  • Dose-response assessment in humans
  • Adduct formation as
    an indicator of exposure
  • Risk assessment
  • Extrapolation from animal studies


  • Analytic methods and tools
  • Gas chromatography (GC)
  • Liquid chromatography (LC)
  • Mass spectrometry (MS)
  • High-resolution mass spectrometry (HRMS)
  • Nuclear magnetic resonance (NMR) spectrometry
  • Ames/Salmonella test
  • Monoclonal antibodies

  • Modeling mutagens from
    creatine
    creatinine
    amino acids
    sugars
  • Heavy isotope incorporation


  • High-performance liquid chromatography (HPLC)
  • Ames/Salmonella test
  • Animal mutation studies
    mice
    Chinese hamster ovary (CHO) cell cultures

  • Cell models
    Mammalian cell systems
    Bacterial cell cultures
  • Enzyme inhibitors




  • Computational chemistry analysis
  • 32P-postlabeling of DNA adducts
  • Accelerator mass spectrometry (AMS)
  • Models
    Whole animals (in vivo)
    Animal cells in culture
    (in vitro)
    Bacterial assays

  • Animal models
    Monkeys
    Rats
    Mice


  • 32P-postlabeling of DNA adducts
  • Accelerator mass spectrometry
  • Epidemiology





  • Return to First Section //Continue On to Next Section