title: Protection against the bacterial mutagenicity of heterocyclic amines by purpurin, a natural anthraquinone pigment.
abstract: Purpurin (1,2,4-trihydroxy-9,10-anthraquinone) is a naturally occurring anthraquinone pigment found in species of madder root. We have found that the presence of purpurin in bacterial mutagenicity assays is responsible for a marked inhibition of mutagenicity induced by food-derived heterocyclic amines. Purpurin was found to be a better inhibitor of Trp-P-2-dependent mutagenicity than either epigallocatechin gallate or chlorophyllin both of which are well-established anti-mutagenic components of diet. Inhibition of Trp-P-2(NHOH) mutagenicity by purpurin was dependent upon pH. It was a better inhibitor in neutral than acidic conditions. Purpurin was protective against the direct mutagen Trp-P-2(NHOH) in both the presence and the absence of hepatic S9 but required pre-incubation. Finally, purpurin was responsible for the inhibition of human CYP1A2 and human NADPH-cytochrome P450 reductase and a decrease in the bioactivation of Trp-P-2 by these enzymes when they were expressed in Salmonella typhimurium TA1538ARO. However, inhibition of Trp-P-2(NHOH)-dependent mutations suggests purpurin also has a direct effect on this mutagen in addition to inhibiting its formation by CYP1A2.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka 1-1-1, Okayama, Japan. marczylo@pharm.okayama-u.ac.jp
authors.forename: T H
authors.initials: TH
authors.lastname: Marczylo
authors.forename: T
authors.initials: T
authors.lastname: Hayatsu
authors.forename: S
authors.initials: S
authors.lastname: Arimoto-Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Tada
authors.forename: K
authors.initials: K
authors.lastname: Fujita
authors.forename: T
authors.initials: T
authors.lastname: Kamataki
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: H
authors.initials: H
authors.lastname: Hayatsu
mesh_terms: D000818:Animals; D000880:Anthraquinones; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001711:Biotransformation; D002243:Carbolines / Q000633:toxicity; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology; D037102:Lectins / Q000494:pharmacology*; D008297:Male; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D000880:Anthraquinones; D016587:Antimutagenic Agents; D002243:Carbolines; D037102:Lectins; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D019388:Cytochrome P-450 CYP1A2; C511975:purpurin anthraquinone