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.
","abstract_html":"<p>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].</p> <p>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.</p> <p>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.</p>","abstract_has_math":false,"creators":["Vance, Robin E."],"institution":null,"degree_name":"Doctor of Philosophy (Medical Science)","degree_level":"Dissertation","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["Robert W. Teel","Raymond G. Hall, Jr.","George Maeda","Elwood S. McCluskey","Allen Strother"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1988,"date_issued":"1988-12-01T08:00:00Z","date_published":"1988-12-01T08:00:00Z","updated_at":"2026-07-24T02:53:44Z","subjects":["Physiology","Diet Benzopyrans; Neoplasms -- etiology; Carcinogens; Breast Neoplasms; Colonic Neoplasms; Dietary Fiber; Dietary Fats"],"languages":["English"],"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."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/1034","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Robert W. Teel","Raymond G. Hall, Jr.","George Maeda","Elwood S. McCluskey","Allen Strother"]},{"key":"dc:creator","label":"Author","values":["Vance, Robin E."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (Medical Science)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Physiology","Diet Benzopyrans; Neoplasms -- etiology; Carcinogens; Breast Neoplasms; Colonic Neoplasms; Dietary Fiber; Dietary Fats"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/1034"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Effect of Dietary Factors on Mutagenesis, Metabolism, and Binding to DNA of Benzo [a] pyrene and Benzo [a] pyrene 7, 8-dihydrodiol"]}]}],"canonical_facts":{"dc:contributor":["Robert W. Teel","Raymond G. Hall, Jr.","George Maeda","Elwood S. McCluskey","Allen Strother"],"dc:creator":["Vance, Robin E."],"dc:description.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.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/1034"],"dc:language":["English"],"dc: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."],"dc:subject":["Physiology","Diet Benzopyrans; Neoplasms -- etiology; Carcinogens; Breast Neoplasms; Colonic Neoplasms; Dietary Fiber; Dietary Fats"],"dc:title":["Effect of Dietary Factors on Mutagenesis, Metabolism, and Binding to DNA of Benzo [a] pyrene and Benzo [a] pyrene 7, 8-dihydrodiol"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (Medical Science)"]},"updated_at":"2026-07-24T02:53:44Z"}