Abstract

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.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

Robert W. Teel

Second Advisor

Raymond G. Hall

Third Advisor

Benjamin H. S. Lau

Fourth Advisor

George Maeda

Fifth Advisor

Allen Strother

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1994

Date (Title Page)

6-1994

Language

English

Library of Congress/MESH Subject Headings

Nitrosamines -- metabolism; Carcinogins -- metabolism; Capsaicin -- pharmacology

Type

Dissertation

Page Count

2 xi; 205

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

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.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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Physiology Commons

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