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

J Agric Food Chem. 2003 May 21;51(11):3334-7. doi: 10.1021/jf026072m.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthraquinones / pharmacology*
  • Anticarcinogenic Agents / pharmacology*
  • Carbolines / pharmacology*
  • Carcinogens / pharmacology*
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP2B1 / metabolism
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA Adducts / analysis
  • DNA Adducts / metabolism*
  • Enzyme Induction / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver / enzymology
  • NADPH-Ferrihemoprotein Reductase / metabolism

Substances

  • Anthraquinones
  • Anticarcinogenic Agents
  • Carbolines
  • Carcinogens
  • DNA Adducts
  • 3-amino-1-methyl-5H-pyrido(4,3-b)indole
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2B1
  • NADPH-Ferrihemoprotein Reductase
  • purpurin anthraquinone