Effect of Dietary Factors on Mutagenesis, Metabolism, and Binding to DNA of Benzo [a] pyrene and Benzo [a] pyrene 7, 8-dihydrodiol
type: CreativeWork
description: 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 inhib…
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 inhib…
author: Vance, Robin E.
language: English
keywords: Physiology, Diet Benzopyrans; Neoplasms -- etiology; Carcinogens; Breast Neoplasms; Colonic Neoplasms; Dietary Fiber; Dietary Fats
date published: 1988-12-01T08:00:00Z
date modified: 2026-07-24T02:53:44Z
provider: Loma Linda University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Loma Linda University