Effect of Dietary Factors on Mutagenesis, Metabolism, and Binding to DNA of Benzo [a] pyrene and Benzo [a] pyrene 7, 8-dihydrodiol

<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>

Name thesis:degree_name

Doctor of Philosophy (Medical Science)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physiology

Year

1988

Author dc:creator

• Vance, Robin E.

Contributors dc:contributor

• Robert W. Teel
• Raymond G. Hall, Jr.
• George Maeda
• Elwood S. McCluskey
• Allen Strother

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

Statement 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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/1034

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2170