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Effect of dietary factors on mutagenesis, metabolism, and binding to DNA of benzo(a)pyrene and benzo(a)pyrene 7,8-dihydrodiol

Thesis/Dissertation ·
OSTI ID:6757129
Ellagic acid (EA), a naturally occurring plant phenol, at concentrations of 5 to 50 {mu}g/plate, inhibited rate 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 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 water-soluble conjugates. At these concentrations EA inhibited the covalent binding of ({sup 3}H) B(a)P and ({sup 3}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-epoxide:deoxyguanosine (BPDE:dG) adducts was inhibited by 13 to 56% for B(a)P 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 metabolite-binding to DNA is not due to the inhibition of S9-mediated metabolism of these compounds. The inhibitory effect may be by previously described scavenging mechanism or by a DNA-affinity binding mechanism that prevents BPDE:DNA adduct formation.
Research Organization:
Loma Linda Univ., CA (USA)
OSTI ID:
6757129
Country of Publication:
United States
Language:
English