Diet has been associated with differences in cancer rates in human populations for many years. However, causes of cancer associated with the diet have not been adequately explained. Since 1980, a series of potent chemicals that cause mutagenic occurrences in bacteria and initiate cancer in animals have been identified. These compounds, known as heterocyclic amines (HA), are formed during the cooking of some foods, most notably, muscle meats. Research into the formation of these carcinogens has shown that certain naturally occurring components of meat—creatine, amino acids, and sugars—react with each other to form HAs when heated to high temperatures. The concentrations of these chemicals in foods are low, from less than one to a few hundred parts-per-billion; however, it is important to know whether a lifetime of consuming HA at these low amounts may inducc cancer in humans. The National Toxicology Program as declared 4 HAs as “Reasonably Expected to Cause Human Cancers.”
Here at Lawrence Livermore National Laboratory, we study the formation of HA during cooking, the absorption of these compounds from ingested foods through the digestive process, their metabolic activation by enzymatic processes to carcinogenic metabolites, and the mechanisms by which they enter the cells and alter the DNA. Our primary means of detection and quantification include high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS). In collaboration with other groups, we utilize some of LLNL's state-of-the-art technology to measure biologically relevant doses of these compounds (Accelerator Mass Spectrometry), to characterize newly isolated mutagens (Liquid Chromatography/Mass Spectrometry; Nuclear Magnetic Resonance), and to image the pathway of heterocyclic amine molecules as they enter the cell (Time of Flight-Secondary Ion Mass Spectrometry).
Cooked meat can contain some of the most mutagenic and carcinogenic molecules known. Docking, molecular dynamics, and quantum mechanical calculations are being used to understand the production of these molecules and their interactions with cytochrome P450.