Approximately one third of all cancer deaths in the United States can be linked to the use of tobacco products. Cessation of smoking is not always an effective prevention method, especially since nicotine is so addictive. For those individuals who continue to use tobacco products, chemoprevention may be an alternative to reduce their cancer risk. We have investigated the chemopreventive efficacy of five phenolic (catechin, ellagic acid, escletin, esculin and propyl gallate) and five non-phenolic (capsaicin, silymarin, diallyl sulfide, tannic acid, and d-limonene) phytochemicals on tobacco-specific nitrosamine (NNK)-induced mutagenesis and NNK metabolism. In the mutagenesis studies, Salmonella typhimuriumstrain TA1535 was used in the Ames/mammalian microsome/mutagenesis assay. In the initial studies, we determined that the optimal conditions for NNK-induced mutagenesis included the use of master plates and agar plates that were less than one week old, saline as a solvent for NNK, 1 mg hamster liver microsomal protein, and minimal DMSO. Experimental results showed that NNK-induced mutagenesis and metabolism of NNK was enhanced by microsomes from both phenobarbitol (PB) and ß-naphthaflavone (ß-NF) treated hamsters and that the effect of the phenolic compounds on NNK-induce mutagenesis depended upon treatment. Ellagic acid was the most efficient inhibitor of NNK-induced mutagenesis by microsomes from untreated animals (controls) while propyl gallate was the most effective inhibitor of mutagenesis by microsomes from PB and ß-NF treated animals. The effect of the phenolic compounds on the microsome-mediated metabolism of NNK correlated with the effect on mutagenesis to some extent. Capsaicin and tannic acid were the most potent inhibitors of NNK-induced mutagenesis of the non-phenolic phytochemicals. Diallyl sulfide was weakly antimutagenic and d-limonene and silymarin had no effect. All five non-phenolic compounds inhibited the α-carbon hydroxylation pathway of NNK metabolism. Studies of the effect of capsaicin on NNK metabolism by microsome from untreated, PB-treated and ß-NF-treated animals showed that capsaicin inhibited the formation of all metabolites of NNK by all microsomal fractions.
Robert W. Teel
Raymond G. Hall
Benjamin H. S. Lau
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Nitrosamines -- metabolism; Carcinogins -- metabolism; Capsaicin -- pharmacology
2 xi; 205
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This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Miller, Cecil Henry, "Inhibition of NNK Mutagenesis and Metabolism by Chemopreventive Phytochemicals" (1994). Loma Linda University Electronic Theses, Dissertations & Projects. 1714.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives