Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by tannic acid, hydroxylated anthraquinones and hydroxylated cinnamic acid derivatives

• Published in: Carcinogenesis (New York) 1985-02, Vol.6 (2), p.237-242
• Main Authors: Huang, Mou-Tuan, Chang, Richard L., Wood, Alexander W., Newmark, Harold L., Sayer, Jane M., Yagi, Haruhiko, Jerina, Donald M., Conney, Allan H.
• Format: Article
• Language: English
• Subjects: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Animals; Anthraquinones - pharmacology; Benzopyrenes - toxicity; Biological and medical sciences; Chemical mutagenesis; Cinnamates - pharmacology; Cricetinae; Cricetulus; Hydrolyzable Tannins - pharmacology; Medical sciences; Mutagens; Polycyclic Compounds - toxicity; Structure-Activity Relationship; Tannins - pharmacology; Toxicology
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/6.2.237

Tannic acid and several hydroxylated anthraquinone and cinnamic acid derivatives inhibited the mutagenic activity of (±)-7β, 8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), an ultimate mutagenic and carcinogenic metabolite of benzo[a]pyrene. The mutagenic activity of 0.05 nmol of B[a]P 7,8-diol-9, 10-epoxide-2 towards strain TA 100 of Salmonella typhimurium was inhibited 50% by incubation of the bacteria and the diol-epoxide with tannic acid (0.5 nmol), anthraflavic acid (7 nmol), rufigallol (7 nmol), quinalizarin (10 nmol), alizarin (30 nmol), purpurin (60 nmol), and danthron (88 nmol). Dose-dependent, but weaker antimutagenic activity was observed for quinizarin, and a number of hydroxylated cinnamic acid derivatives. Gallic acid and m-digallic acid, major components of tannic acid, possessed < 1% of the antimutagenic activity of tannic acid, although m-digallic acid was over 3 times more active than gallic acid. The antimutagenic activity of tannic acid was a result of its interaction with B[a]P 7,8-diol-9, 10-epoxide-2 since the rate of disappearance of the diol-epoxide from cell-free solutions in 1: 9dioxane:water was markedly stimulated by the polyphenol. Tannic acid was a highly potent inhibitor of the mutagenic activity of the bay-region diol-epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene and dibenzo[a,i]pyrene, but higher concentrations of tannic acid were needed to inhibit the mutagenicity of the chemically less reactive benzo[a]-pyrene 4,5-oxide and the bay-region diol-epoxides of benz[a]-anthracene, chrysene and benz[c]phenanthrene.