| AUTHOR: |
|
Wood AW, Huang MT, Chang RL, Newmark HL, Lehr RE, Yagi H, Sayer JM,
Jerina DM, Conney AH |
| ABSTRACT: |
|
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. One nmol of ellagic acid in the 0.5-ml
incubation mixture inhibits the mutagenicity of 0.05 nmol of B[a]P
7,8-diol,9,10-epoxide-2 in strain TA100 of Salmonella typhimurium. 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. Similar to results obtained with the bacteria,
ferulic, caffeic, and chlorogenic acids are approx two orders of magnitude
less active than ellagic acid in the mammalian cell assay. In parallel
with the mutagenicity studies, ellagic acid is 80-300x more effective than
the other phenols in accelerating the disappearance of B[a]P
7,8-diol-9,10-epoxide-2. 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
ulimate 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. (42 Refs) |