title: Evaluation of the mutagenicity and antimutagenicity of forty-two 3-substituted flavones in the Ames test.
abstract: The mutagenic and antimutagenic activities of forty-two synthetic flavones were assessed by the Ames test. The tested flavones included twenty-three 3-nitroflavones, eighteen 3-aminoflavones and the 3-chloroflavone. The mutagenicity was evaluated with Salmonella typhimurium TA100 and YG1042 (an overproducing nitroreductase and O-acetyltransferase TA100 strain) with and without metabolic activation (S9 mix). The antimutagenicity of the non mutagenic derivatives was evaluated against 11 known reference mutagens. A total of 39 synthetic flavones were mutagenic. The mutagenic activities ranged from 0.1 rev/nmole (4'-chloro-6-methoxy-3-nitroflavone) to 6240 rev/nmole (4'-methoxy-3, 3'-diaminoflavone). Two differences were found between the 3-amino and the 3-nitroflavones: (i) the mutagenicity of the 3-aminoflavones required the presence of the metabolic activation; (ii) the 3-amino derivatives were more mutagenic than their 3-nitro counterparts. Increased mutagenicity, as assessed with strain YG1042, was limited to 17/39 derivatives. The mutagenic activity was induced by the presence of the double bond at the 2,3-position for conjugation of the lone-pair electron with the carbonyl group on the 'C' ring. This mutagenicity was modulated by substituents at the 2'-position. Additional mutagenicity was brought by the aminoaromatic and nitroaromatic group reduction by bacterial nitroreductases and by the S9 mix; it was modulated by different substituents on the aromatic rings of the flavones. Three flavones: 3-chloroflavone (1C), 4'-hydroxy-3-nitroflavone (23N) and 2',3-diaminoflavone (2A) showed antimutagenic properties. Compound 1C was efficient against benzo(a)pyrene (BaP), 2-aminofluorene (2AF), 2-aminoanthracene (2AA), 4-nitroquinoline-1-oxide (4NQO) and 1-methyl-3'-nitro-1-nitrosoguanidine (MNNG). Compound 23N inhibited the mutagenicity of BaP and MNNG. The antimutagenic activity of 2A was limited to MNNG.
authors.affiliation: Laboratoire de Biogénotoxicologie et Mutagénèse Environnementale (EA 1784), Université de la Méditerranée, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385, Marseille Cedex 05, France.
authors.forename: C
authors.initials: C
authors.lastname: Beudot
authors.forename: M P
authors.initials: MP
authors.lastname: De Méo
authors.forename: D
authors.initials: D
authors.lastname: Dauzonne
authors.forename: R
authors.initials: R
authors.lastname: Elias
authors.forename: M
authors.initials: M
authors.lastname: Laget
authors.forename: H
authors.initials: H
authors.lastname: Guiraud
authors.forename: G
authors.initials: G
authors.lastname: Balansard
authors.forename: G
authors.initials: G
authors.lastname: Duménil
mesh_terms: D016587:Antimutagenic Agents / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology* / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D016587:Antimutagenic Agents; D005419:Flavonoids; D009153:Mutagens