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Inhibition of benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol metabolism and DNA binding in mouse lung explants by ellagic acid.
Dixit R; Teel RW; Daniel FB; Stoner GD
Cancer Res 1985 Jul; 45(7):2951-2956
The effect of ellagic-acid (476664) on in-vitro metabolism of benzo(a)pyrene (50328) (BaP) or trans-7,8-dihydro-7,8- dihydroxybenzo(a)pyrene (trans BaP) by mouse lung explants was investigated. Explants were cultured for 16 hours in the presence or absence of 10 to 100 micromolar (microM) concentrations of the naturally occuring plant phenol. Ellagic-acid was then removed and explants were incubated with 1microM tritiated BaP or trans BaP for 24 hours. Or ellagic-acid was also added during incubation with BaP. Explant DNA was isolated using hydroxylapatite chromatography, and the BaP metabolites in the medium were analyzed by high pressure liquid chromatography. Pretreatment with 10 to 100microM ellagic- acid resulted in a 21 to 38 percent inhibition of the binding of BaP metabolites to DNA. Ellagic-acid at 100microM concentrations was not more inhibitory than at 50microM. When ellagic-acid was added during BaP incubation, DNA showed a dose dependent 18 to 71 percent inhibition in the binding of BaP metabolites. Pretreatment with 10, 25, 50, or 100microM ellagic-acid resulted in a 52, 65, 70, and 65 percent inhibition of binding of trans BaP metabolites to DNA, respectively. Treatment with 100microM ellagic-acid reduced adduct formation 70 to 80 percent. The inhibition of BaP metabolism by mouse lung explants was indicated by a concentration dependent decrease in the amount of total metabolites and a concomitant increase in unmetabolized BaP in the medium. Unmetabolized trans BaP was increased 7.2 to 20.3 percent, depending on ellagic-acid concentration while total metabolites were decreased 7.7 to 19.9 percent. The authors conclude that ellagic-acid inhibits the covalent binding of BaP metabolites to the DNA of mouse lung explants when added to the medium prior to or together with BaP. The binding of trans BaP is inhibited to a greater degree than that of BaP itself.
NIOSH-Author; Animal-studies; Chemical-analysis; Cancer; Body-distribution; Exposure-levels; Carcinogenicity; Analytical-models; Lung-lesions
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