Inhibition of polycyclic aromatic hydrocarbon-DNA adduct formation in epidermis and lungs of SENCAR mice by naturally occurring plant phenols.

M Das, W A Khan, P Asokan, D R Bickers, H Mukhtar

Index: Cancer Res. 47(3) , 767-73, (1987)

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Abstract

Naturally occurring plant phenols such as tannic acid, quercetin, myricetin, and anthraflavic acid are known to inhibit the mutagenicity of several bay-region diol-epoxides of polycyclic aromatic hydrocarbons (PAHs). The binding of bay-region diol-epoxides of PAHs to target tissue DNA is thought to be essential for the initiation of cancer by these compounds. In this study we investigated the effect of these plant phenols on PAH-DNA adduct formation in the epidermis and lung of SENCAR mice. In vitro addition of tannic acid, quercetin, myricetin, and anthraflavic acid (25 microM) to an incubation system containing epidermal microsomes prepared from either control or 3-methylcholanthrene-pretreated mice inhibited benzo(a)pyrene binding to calf thymus DNA by 63-64, 38-43, 36-37, and 27-33%, respectively. A single topical application of tannic acid, quercetin, myricetin, and anthraflavic acid at a dose of 400 mumol/kg body weight resulted in the inhibition of [3H]benzo(a)pyrene binding to epidermal DNA (48-73%) and protein (51-63%). The same dose of these plant phenols (400 mumol/kg) caused even greater inhibition of (+/-)-[3H]-7 beta,8 alpha-dihydroxy-7,8-dihydrobenzo(a)pyrene and [3H]-7,12-dimethybenz(a)anthracene binding to epidermal DNA and protein. The formation of (+)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene-deoxyguanosine adducts was substantially diminished in both epidermis (62-86%) and lungs (38-84%). These results indicate that tannic acid, quercetin, myricetin, and anthraflavic acid are potent inhibitors of carcinogen binding to epidermal and lung DNA and suggest that these plant phenols could prove useful in modifying the risk of tumor induction by PAHs such as benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in these two tissues.