Abstract
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
Physiology
Department
Physiology
School
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
Ph.D.
Year Degree Awarded
1988
Date (Title Page)
12-1988
Language
English
Library of Congress/MESH Subject Headings
Diet Benzopyrans; Neoplasms -- etiology; Carcinogens; Breast Neoplasms; Colonic Neoplasms; Dietary Fiber; Dietary Fats
Type
Dissertation
Page Count
vii; 131
Digital Format
Digital Publisher
Loma Linda University Libraries
Copyright
Author
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.
Recommended Citation
Vance, Robin E., "Effect of Dietary Factors on Mutagenesis, Metabolism, and Binding to DNA of Benzo [a] pyrene and Benzo [a] pyrene 7, 8-dihydrodiol" (1988). Loma Linda University Electronic Theses, Dissertations & Projects. 1034.
https://scholarsrepository.llu.edu/etd/1034
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