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Ellagic acid toxicity and interaction with benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol in human bronchial epithelial cells

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Abstract

Ellagic acid, a plant phenol present in various foods consumed by humans, has been reported to have both anti-mutagenic and anti-carcinogenic potential. To evaluate the potential anti-carcinogenic property of ellagic acid, we tested its effects on the toxicity of ben-zo[a]pyrene and benzo[a]pyrene, 7,8-dihydrodiol and binding of benzo[a]yrene to DNA in cultured human bronchial epithelial cells. The toxicity of ellagic acid itself for human bronchial epithelial cells was also determined. Using a colony-forming efficiency assay, it was found that a nontoxic concentration of ellagic acid (5 μg/ml) enhanced the toxicity of benzo[a]pyrene.7,8-dihydrodiol in human bronchial epithelial cells. In contrast, ellagic acid at concentrations of l.5 and 3.0 μg/ml inhibited binding of benzo[a]pyrenemetabolites to DNA in these cells. An explanation for the potentiating effect of ellagic acid on the toxicity of benzo[a]pyrene, 7,8-dihydrodiol will require further investigation into the possible mechanisms of interaction between these two compounds.

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Abbreviations

B[a]P:

benzo[a]pyrene

B[a]P 7,8-DHD:

(±)trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene

B[a]PDE-1:

(±)-7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene

B[a]PDE-2:

(±) 7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene

B[a]PDE-1:dG:

N2-]10{7β,8β,9α-dihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene]yl}:deoxyguanosine

B[a]PDE-2:dG:

NZ-{10α-[7β,8α,9β-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene]yl}:deoxyguanosine

CFE:

colony forming efficiency

EA:

ellagic acid

HBE:

human bronchial epithelial

References

  • BABCOCK, M.S., MARINO, M., GUNNING, W.T. and STONER, G.D. (1983). Clonal growth and serial propagation of rat esophageal epithelial cells. In Vitro 19:403–415.

    Google Scholar 

  • DEL TITO, B.J., MUKHTAR, H. and BICKERS, D.R. (1983). Inhibition of epidermal metabolism and DNA-binding of benzo[a]pyrene by ellagic acid. Biochem. Biophys. Res. Commun. 114:388–394.

    Google Scholar 

  • DIXIT, R., TEEL, R.W., DANIEL, F.B. and STONER, G.D. (1985). Inhibition of benzo[a]pyrene and benzo[a]pyrene-trans-7,8-diol metabolism and DNA binding in mouse lung explants by ellagic acid. Cancer Res. 45:2951–2956.

    Google Scholar 

  • KIRBY, K.S. (1965). Isolation and characterization of ribosomal ribonucleic acid. Biochem. J. 96:266–269.

    Google Scholar 

  • LECHNER, J.F., BABCOCK, M.S., MARNELL, M., NARAYAN, K.S. and KAIGHN, M.E. (1980). Normal human prostate epithelial cell cultures. In: Methods and Perspectives in Cell Biology (C.C. Harris, B.F. Trump and G.D. Stoner, Eds.),185–191. Academic Press, New York.

    Google Scholar 

  • LESCA, P. (1983). Protective effects of ellagic acid and other plant phenols on benzo[a]pyreneinduced neoplasia in mice. Carcinogenesis 4:1651–1653.

    Google Scholar 

  • MILLER, B.C. and MILLER, J.A. (1976). The metabolism of chemical carcinogens to reactive electrophiles and their possible mechanisms of action in carcinogenesis. In: Chemical Carcinogenesis Monograph 173(C.E. Searle, Ed.), 737–762. American Chemical Soc., Washington, DC.

    Google Scholar 

  • MUKHTAR, H., DAS, M., DEL TITO, B.J. and BICKERS D.R. (1984). Protection against 3-methylcholanthrene-induced skin tumorigenesis in BALB/c mice by ellagic acid. Biochem. Biophys. Res. Commun. 119:751–757.

    Google Scholar 

  • MUKHTAR, H., DAS, M. and BICKERS, D.R. (1985). Protection against 3-methylcholanthrene-induced skin tumorigenesis in BALB/c mice by chronic oral feeding of ellagic acid. Fed. Proc. 44:411.

    Google Scholar 

  • NEWMARK, H.L. (1984). A hypothesis for dietary, components as blocking agents of chemical carcinogenesis: plant phenolics and pyrrole pigments. Nutr. Cancer 6:58–70.

    Google Scholar 

  • PEEHL, D.M. and HAM, R.G. (1980). Clonal growth of human keratinocytes with small amounts of dialyzed serum. In Vitro 16:526–540.

    Google Scholar 

  • SAYER, J.M., YAGI, H., WOOD, A.W., CONNEY, A.H. and JERINA, D.M. (1982). Extremely facile reaction between the ultimate carcinogen benzo[a]pyrene-7,8-diol 9,10-epoxide and ellagic acid. J. Am. Chem. Soc. 104:5562–5564.

    Google Scholar 

  • SIMS P., GROVER, P.L., SWAILAND, A., PAL, K. and HEWER, A. (1974). Metabolic activation of benzo[a]pyrene proceeds by a diol epoxide. Nature 252:326–328.

    Google Scholar 

  • STONER, G.D., DANIEL, F.B., SCHENK, K.M., SCHUT, H.A.J., GOLDBLATT, P.J. and SANDWISCH, D.W. (1982). Metabolism and DNA binding of benzo[a]pyrene in cultured human bladder and bronchus. Carcinogenesis 3:195–201.

    Google Scholar 

  • TEEL, R.W., DIXIT, R. and STONER, G.D. (1985). The effect of ellagic acid on the uptake, persistence, metabolism and DNA-binding of benzo[a]pyrene in cultured explants of strain A/J mouse lung. Carcinogenesis 6:391–395.

    Google Scholar 

  • TEEL, R.W., STONER, G.D., BABCOCK, M.S., DIXIT, R. and KIM, K. (in press). Benzo[a]pyrene metabolism and DNA-binding in cultured explants of human bronchus and in monolayer cultures of human bronchial epithelial cells treated with ellagic acid. Cancer Prevention and Detection.

  • TSAO, M.D., WALTHALL, B.J. and HAM, R.G. (1982). Clonal growth of normal human epithelial keratinocytes in a defined medium. J. Cell Physiol. 110:219–229.

    Google Scholar 

  • WOOD, A.W., HUANG, M.T., CHANG, R.L., NEWMARK, H.L., LEHR, R.E., YAGI, H., SAYER, J. M., JERINA, D. M. and CONNEY, A. H. (1982). Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: exceptional activity of ellagic acid. Proc. Natl. Acad. Sci., USA. 79:5513–5517.

    Google Scholar 

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Teel, R.W., Babcock, M.S., Dixit, R. et al. Ellagic acid toxicity and interaction with benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol in human bronchial epithelial cells. Cell Biol Toxicol 2, 53–62 (1986). https://doi.org/10.1007/BF00117707

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