Document Detail

Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: exceptional activity of ellagic acid.
MedLine Citation:
PMID:  6752950     Owner:  NLM     Status:  MEDLINE    
Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (+/-)-7beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. The mutagenicity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 in strain TA100 of Salmonella typhimurium is inhibited 50% by incubation of the bacteria and the diol epoxide with 150 nmol of ferulic acid, 75 nmol of caffeic acid, 50 nmol of chlorogenic acid or, most strikingly, 1 nmol of ellagic acid in the 0.5-ml incubation mixture. A 3-nmol dose of ellagic acid inhibits mutation induction by 90%. Ellagic acid is also a potent antagonist of B[a]P 7,8-diol-9,10-epoxide-2 in Chinese hamster V79 cells. Mutations to 8-azaguanine resistance induced by 0.2 muM diol epoxide are reduced by 50% when tissue culture media also contains 2 muM ellagic acid. Similar to results obtained with the bacteria, ferulic, caffeic, and chlorogenic acids are approximately two orders of magnitude less active than ellagic acid in the mammalian cell assay. The antimutagenic effects of the plant phenols result from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2, because a concentration-dependent increase in the rate of diol epoxide disappearance in cell-free solutions of 1:9 dioxane/water, pH 7.0, is observed with all four phenols. In parallel with the mutagenicity studies, ellagic acid is 80-300 times more effective than the other phenols in accelerating the disappearance of B[a]P 7,8-diol-9,10-epoxide-2. Ellagic acid at 10 muM increases the disappearance of B[a]P 7,8-diol-9,10-epoxide-2 by approximately 20-fold relative to the spontaneous and hydronium ion-catalyzed hydrolysis of the diol epoxide at pH 7.0. Ellagic acid is a highly potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene, and dibenzo[a,i]pyrene, but higher concentrations of ellagic acid are needed to inhibit the mutagenic activity of the chemically less reactive bay-region diol epoxides of benz[a]anthracene, chrysene, and benzo[c]phenanthrene. These studies demonstrate that ellagic acid is a potent antagonist of the adverse biological effects of the ultimate carcinogenic metabolites of several polycyclic aromatic hydrocarbons and suggest that this naturally occurring plant phenol, normally ingested by humans, may inhibit the carcinogenicity of polycyclic aromatic hydrocarbons.
A W Wood; M T Huang; R L Chang; H L Newmark; R E Lehr; H Yagi; J M Sayer; D M Jerina; A H Conney
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  79     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1982 Sep 
Date Detail:
Created Date:  1982-12-21     Completed Date:  1982-12-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5513-7     Citation Subset:  IM    
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MeSH Terms
Cell Line
Cell Survival / drug effects
Epoxy Compounds / pharmacology*
Ethers, Cyclic / pharmacology*
Mutagenicity Tests
Phenols / pharmacology*
Plants, Medicinal*
Polycyclic Compounds / pharmacology*
Salmonella typhimurium / drug effects
Structure-Activity Relationship
Reg. No./Substance:
0/Epoxy Compounds; 0/Ethers, Cyclic; 0/Mutagens; 0/Phenols; 0/Polycyclic Compounds

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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