Protection against Trp-P-2 DNA adduct formation in C57bl6 mice by purpurin is accompanied by induction of cytochrome P450.

Tim Marczylo, Chitose Sugiyama, Hikoya Hayatsu

Index: J. Agric. Food Chem. 51(11) , 3334-7, (2003)

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Abstract

Purpurin, an anthraquinone constituent from madder root, has previously been reported as antimutagenic in the Ames Salmonella bacterial mutagenicity assay and as antigenotoxic in Drosophila melanogaster, against a range of environmental carcinogens. Short-term dietary supplementation with purpurin inhibits the formation of hepatic DNA adducts in male C57bl6 mice after a single dose of the heterocyclic amine dietary carcinogen Trp-P-2 (30 mg/kg). Inhibition of adduct formation was dose-dependent. No DNA adducts were observed in animals treated only with purpurin. The decrease in adduct formation was accompanied by significant, dose-dependent inductions of hepatic cytochrome P450-dependent dealkylations of methoxy- (CYP1A2), ethoxy- (CYP1A1), and pentoxy- (CYP2B) resorufins, total cytochrome P450, and NADPH cytochrome P450 reductase. It is hypothesized that purpurin exhibits chemopreventive potential by inhibiting the cytochrome P450-dependent metabolism of heterocyclic amines to their genotoxic N-hydroxylamines.