Colon cancer is one of the two most common organ-site cancers in the world, and over 50,000 people per year die in the United States alone from this disease. It is suspected that various mutagens consumed in human foods (either naturally occurring or produced on cooking) may contribute to the incidence of colon cancer. The human intestinal tract is the largest surface area of our body next to our lungs that is in constant contact with the external environment, and in this case the external environment has as high a concentration of bacteria as any place on earth. One strong probability is thus that these intestinal bacteria interact with the mutagens to modify them in some way. Such modifications could be beneficial, making the mutagens less mutagenic, or harmful, making them more mutagenic. A proper assessment of the risk from food mutagens thus requires a knowledge of their interaction with intestinal bacteria, and the long-term objectives of the proposed research are thus to provide the basis for this accurate risk assessment. In addition, if the metabolism turns out to be harmful, the research may indicate ways to reduce or eliminate the harmful metabolic processes.
The specific aims of the project are to determine the anaerobic metabolism of the three point fried-food mutagens, IQ, Trp-P-2, and Glu-P-1. These mutagens will be prepared in radiolabeled form and then incubated with a variety of anaerobic micro-organisms. The metabolic products will be detected by radiochromatography, and isolated by HPLC, and their structure will be determined by spectroscopic techniques, especially FAB mass spectrometry. The major metabolic products will then be synthesized and tested to determine their mutagenic activity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040821-02
Application #
3181109
Study Section
(SSS)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Virginia Polytechnic Institute and State University
Department
Type
Schools of Arts and Sciences
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24060
Weisburger, J H; Rivenson, A; Kingston, D G et al. (1995) Dietary modulation of the carcinogenicity of the heterocyclic amines. Princess Takamatsu Symp 23:240-50
Weisburger, J H; Rivenson, A; Reinhardt, J et al. (1994) Genotoxicity and carcinogenicity in rats and mice of 2-amino-3,6-dihydro-3-methyl-7H-imidazolo[4,5-f]quinolin-7- one: an intestinal bacterial metabolite of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline. J Natl Cancer Inst 86:25-30
Shu, Y Z; Kingston, D G; Van Tassell, R L et al. (1991) Metabolism of 1,4-dinitro-2-methylpyrrole, a mutagen formed by a sorbic acid-nitrite reaction, by intestinal bacteria. Environ Mol Mutagen 17:181-7
Shu, Y Z; Kingston, D G; Van Tassell, R L et al. (1991) Metabolism of levamisole, an anti-colon cancer drug, by human intestinal bacteria. Xenobiotica 21:737-50
Van Tassell, R L; Kingston, D G; Wilkins, T D (1990) Metabolism of dietary genotoxins by the human colonic microflora;the fecapentaenes and heterocyclic amines. Mutat Res 238:209-21
Van Tassell, R L; Kingston, D G; Wilkins, T D (1990) Dietary genotoxins and the human colonic microflora. Prog Clin Biol Res 340E:149-58
Carman, R J; Van Tassell, R L; Kingston, D G et al. (1988) Conversion of IQ, a dietary pyrolysis carcinogen to a direct-acting mutagen by normal intestinal bacteria of humans. Mutat Res 206:335-42
Bashir, M; Kingston, D G; Carman, R J et al. (1987) Anaerobic metabolism of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) by human fecal flora. Mutat Res 190:187-90