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Diet and Cancer How Cooked Meats Might Be Involved

Diet and Cancer How Cooked Meats Might Be Involved. Mark Knize Biosciences Research Program, LLNL. UCRL-PRES-219636. Age Adjusted Cancer Rates, All Sites Combined. Male. Female. COUNTRY RATE Hungary 129.4 England & Wales 126.9 New Zealand 124.3 Czechoslovakia 119.9

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Diet and Cancer How Cooked Meats Might Be Involved

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  1. Diet and CancerHow Cooked Meats Might Be Involved Mark Knize Biosciences Research Program, LLNL UCRL-PRES-219636

  2. Age Adjusted Cancer Rates, All Sites Combined Male Female COUNTRY RATE Hungary 129.4 England & Wales 126.9 New Zealand 124.3 Czechoslovakia 119.9 Uruguay 118.3 United States 109.7 Sweden 98.6 USSR 92.9 France 89.9 Ecuador 86.1 Mexico 78.2 Japan 78.1 Thailand 36.4 COUNTRY RATE Hungary 235.4 Czechoslovakia 228.9 France 204.7 Uruguay 202.5 USSR 193.1 England & Wales 181.9 New Zealand 171.8 United States 163.2 Japan 149.8 Sweden 127.7 Ecuador 83.9 Mexico 77.3 Thailand 54.4 0 0 50 100 150 200 250 50 100 150 200 250

  3. U.S. Cancer Mortality, 1950-1990

  4. Mutation TATGCGT TATACGT Cancer Pathway at the Chemical Level Formation Absorption Metabolism Enzyme Enzyme DNA Adduction DNA Cancer

  5. Genetic and acquired susceptibility • Lifestyle Cooking Practices Gender and Ethnicity Genetic polymorphisms Environmental Exposures Diet Occupation Age What affects the “cancer pathway”?

  6. Steps in Chemical Carcinogenesis Carcinogen enzymes Reactive chemical enzymes Mutation Binds to DNA repair? Causes a permanent mistake (mutation) Leads to tumor

  7. Ames test for Mutagenic Activity • Combine: • 108 bacteria • Test chemical or mixture • Rat liver enzymes

  8. It was found that there are mutagens meat 25 Years Ago • These extracts are mutagenic in bacteria

  9. Salmonella amino acid sequence Wild type hisD3052 gene: ...CGC GCG GAC ACC GCC CGG CAG GCC CTG… …Arg Ala Asp Thr Ala Arg Gln Ala Leu… Test strain: ...ACC GCC GGC AGG CCC TGA... ...Thr Ala Gly Arg Pro END Revertant: ...CGC GGA CAC CGC CGG CAG GCC CTG… ...Arg Gly His Arg Arg Gln Ala Leu… A deletion of 3n-1 corrects reading frame C GC

  10. Formation of Mutagenic Activity in Fried Beef Patties

  11. Mutagenic Activity of Cigarette Smoke Brand Revertant colonies per gram burned Camel filtered 62,300 Camel unfiltered 63,300 Marlboro filtered 59,800 Lucky unfiltered 58,300 GPC filtered 56,000 GPC unfiltered 56,500 M.F. West and Tracy H.S. 1998

  12. Mutagenic activity of a smokeless tobacco extract y = 0.7592x + 22.343 R = 0.963 2 120 100 80 60 40 20 0 0 50 100 150 µl sample Jenni Watt, Tracy High School, 1998

  13. Mutagenic Activity of Non-muscle Foods Sample Revertants per gram Bagel, as purchased Not positive* Bagel, toasted 2.7 Bagel, over toasted 19.8 Hamburger, 220°C 437 * No doubling of background observed M Blakley, 1994 Peanut butter, aflatoxin levels are required by law to be below 5 ng/g (p.p.b.) (about 1500 revertants per gram).

  14. Chromatography-Separating Mixtures

  15. How do we measure compounds in foods?

  16. HPLC (High Performance Liquid Chromatograph)- Separation, Elution and Detection How do we measure compounds?

  17. Are we exposed to food mutagens?

  18. Formation of the cooked-meat mutagen PhIP

  19. Intake of PhIP and Tumor Incidence From Shirai et al. 1995

  20. Marinade the meat before cooking Lower the cooking temperature and reduce the cooking time Microwave food and pour off juices before cooking Flip frequently during cooking How can we reduce cooked meat carcinogen formation?

  21. Meat patty Microwave cook 2 min Meat Liquid (water, fat, carcinogen precursors) Cook by frying Discard Meat with 10% of the carcinogens Microwave Pretreatment of Meat Patties

  22. Effect of Microwave Pretreatment on Heterocyclic Amine Formation Nanograms HA per gram cooked weight

  23. The Effect of Marinating on Heterocyclic Amine Formation Nanograms HA per gram cooked weight

  24. Heterocyclic amines formed in pan-fried beef patties 25 Turn once Turn every minute 20 15 Heterocyclic amines, ng/g 10 5 0 140 160 180 200 220 240 260 Pan temperature, °C Cooking processes involve 3 forms of heat flow that can be mathematically described q = k A (T1-T2) q = sA (T41 - T42 ) Convection Radiation Conduction q: heat flow k: thermal conductance (convective or conductive) s: Stefan-Boltzmann const. A: surface area T1, T2: Temperatures

  25. To show an effect in humans, the factor being studied needs to have: • Statistical strength • Consistency • A dose response • Biological plausibility

  26. Human Studies of Meat and Colorectal Cancer (7 of 30 shown) Ng=Not given Nutrition Reviews, Knize and Felton,2006

  27. Individual susceptibility

  28. Conclusion from our studies: Avoid over-cooked meat!

  29. Cooked meat mutagens on 20/20

  30. Acknowledgements: • Jim Felton (Scientific Director) • Susan Fortson • Cyndy Salmon • Kristen Kulp Funding: National Institutes of Health DOD Prostate Cancer Research Program CA Breast Cancer Research This work was performed under the auspices of the U.S. DOE by LLNL under contract no. W-7405-Eng-48 UCRL-PRES-219636

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