Ellagic acid (EA), a naturally occurring plant phenol, at concentrations of 5 to 50 pg/plate, inhibited rat liver S9 protein dependent benzo[a]pyrene (B[a]P)-induced mutagenesis in Salmonella typhimurium TA 100 by 30-81% and B[a]P 7,8-dihydrodiol (DHD)-induced mutagenesis by 29 to 75%. EA (5-40 juM) did not significantly affect the metabolism of B[a]P or B[a]P 7,8-DHD as determined by high performance liquid chromatographic analysis of the organosoluble fraction and by the quantification of watersoluble conjugates. At these concentrations EA inhibited 3 3 the covalent binding of [ H] B[a]P and [ H] B[a]P 7,8-DHD metabolites to calf thymus DNA by 5 to 42% and 27 to 64%, respectively. Formation of benzo[a]pyrene 7,8-dihydrodiol- 9,10-epoxideideoxyguanosine (BPDErdG) adducts was inhibited by 13 to 56% for B[a]P and 11 to 38% for B[a]P 7,8-DHD. These results suggest that the antimutagenic effect of EA and its inhibition of B[a]P and B[a]P 7,8-DHD metabolitebinding to DNA is not due to the inhibition of S9-mediated metabolism of these compounds. The inhibitory effect may be by a previously described scavenging mechanism [43] or by a DNA-affinity binding mechanism that prevents BPDE:DNA adduct formation [58, 95].

At concentrations of 5 to 50 pg/plate tannic acid (TA), a mixture of digallic acid esters of glucose, inhibited B[a]P-induced mutagenesis in Salmonella typhimurium TA 100 by 32 to 77%. TA (10-40 jiM) did not inhibit the formation of organosoluble metabolites of B[a]P or water-soluble conjugates of B[a]P; however, it inhibited B[a]P metabolitebinding to DNA by as much as 40% and inhibited BPDE:dG adduct formation by 12 to 54%. These results suggest that the antimutagenic effect of TA and the inhibition of B[a]P metabolite-binding to DNA is not due to an inhibition of B[a]P metabolism. The mechanism of inhibition appears similar to those suggested for EA.

Hepatic microsomes from rats which had been given 30% glucose in drinking water 48 hrs prior to sacrifice inhibited B[a]P-induced mutagenesis by 27% and B[a]P 7,8- DHD-induced mutagenesis by 55% in Salmonella tvphimurium TA 100. Microsomes from glucose-treated rats inhibited B[a]P and B[a]P 7,8-DHD metabolite-binding to calf thymus by 17 and 20% respectively and BPDE:dG adduct formation was inhibited by 38 and 50% respectively. Since the amount of inhibition of mutagenesis and BPDE:dG adduct formation corresponds to the glucose-mediated inhibition of metabolism of B[a]P and B[a]P-7,8-DHD, the data suggest that the major mechanism by which glucose exerts its antimutagenic effect is by inhibition of the microsome-mediated metabolism of B[a]P and B[a]P 7,8-DHD.

LLU Discipline





Graduate School

First Advisor

Robert W. Teel

Second Advisor

Raymond G. Hall, Jr.

Third Advisor

George Maeda

Fourth Advisor

Elwood S. McCluskey

Fifth Advisor

Allen Strother

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level


Year Degree Awarded


Date (Title Page)




Library of Congress/MESH Subject Headings

Diet Benzopyrans; Neoplasms -- etiology; Carcinogens; Breast Neoplasms; Colonic Neoplasms; Dietary Fiber; Dietary Fats



Page Count

vii; 131

Digital Format


Digital Publisher

Loma Linda University Libraries

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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.


Loma Linda University Electronic Theses and Dissertations

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

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