The Ames/Salmonella and CHO mammalian cell assays will be used to assess the cytotoxicity and mutagenicity of various heterocyclic amines. The Ames/Salmonella assay will be used to detect the mutagenic activity of food extracts and to guide the purification of new mutagens from flame-cooked beef. The mutation-lowering effects of the flavonoid apigenin and 11 isomers on MeIQx and PhIP will be evaluated using the Ames test. The mutagenicity of PhIP, IQ and MeIQx will be studied in the Ames test using a variety of UDP-glucuronosyltransferase expressing microsomes as the activating system. The Ames test will also be used to screen the mutagenic potency of ten 2-aminoimidazole-azaarene (AIA) compounds and their respective N-hydroxy derivatives. The genetically modified CHO cells will be used to assess the cytotoxicity and mutagenicity of the recently characterized IFP, as well as any additional newly isolated compounds. Cytogenetic end points of SCEs and chromosomal aberrations with IFP and other compounds will also be evaluated using the CHO cells. The core will also assist in evaluating the cytotoxicity and mutagenicity of the cell line expressing UDPglucuronosyltransferase 1A1 gene after it is developed. This CHO mammalian assay is not only a more sensitive system for evaluating the differential cytotoxicity and mutagenicity of compounds, but it is also a better system for understanding the mutagenic mechanism. This core will also be involved in methods monitoring the survival of E.coli K12 in food at different cooking temperatures after various methods of cooking.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA055861-09A2
Application #
6617084
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2002-04-19
Project End
2007-01-31
Budget Start
Budget End
Support Year
9
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Lawrence Livermore National Laboratory
Department
Type
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
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Bogen, K T; Keating 2nd, G A; Chan, J M et al. (2007) Highly elevated PSA and dietary PhIP intake in a prospective clinic-based study among African Americans. Prostate Cancer Prostatic Dis 10:261-9
Keating, Garrett A; Bogen, Kenneth T; Chan, June M (2007) Development of a meat frequency questionnaire for use in diet and cancer studies. J Am Diet Assoc 107:1356-62
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Bogen, K T; Enns, L; Hall, L C et al. (2001) Gel microdrop flow cytometry assay for low-dose studies of chemical and radiation cytotoxicity. Toxicology 160:5-10
Keating, G A; Bogen, K T (2001) Methods for estimating heterocyclic amine concentrations in cooked meats in the US diet. Food Chem Toxicol 39:29-43
Hatch, F T; Knize, M G; Colvin, M E (2001) Extended quantitative structure-activity relationships for 80 aromatic and heterocyclic amines: structural, electronic, and hydropathic factors affecting mutagenic potency. Environ Mol Mutagen 38:268-91
Hatch, F T; Lightstone, F C; Colvin, M E (2000) Quantitative structure-activity relationship of flavonoids for inhibition of heterocyclic amine mutagenicity. Environ Mol Mutagen 35:279-99
Matsumoto, K; Tucker, J D (1998) Detection of structural chromosome damage in rat interphase cells using region-specific fluorescence in situ hybridization probes developed by microdissection. Mutat Res 421:179-90

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