title: Genotoxicity of industrial dyes under the inductive effect of ethanol on monooxygenase system in mice.
abstract: The genotoxic effects of triarylmethane (Acid Green 16, C.I.44025) and arylmonoazo (Basic Orange 28, developed by Boruta Pigment Plant, Poland, C.I. undisclosed) dyes, were evaluated in Balb/C mice. Animals were fed for 6 days nutritionally adequate Portagen liquid diet (1 kcal/ml) or isocaloric alcoholic diet containing 5% (w/v) ethanol (36% of total calories) in order to induce the cytochrome P-4502E1 monooxygenase. Dye compounds were administered intraperitoneally 30 h before the test at doses: 90 mg/kg of Acid Green 16 and 70 mg/kg of Basic Orange 28. Bone marrow micronucleus test was used for evaluation of genotoxicity of the dyes. Ethanol caused an increase of the level of cytochrome P-450 by 200% and activities of 7-ethoxycoumarin O-deethylase (ECOD) by 650%, 7-ethoxyresorufin O-deethylase (EROD) by 460% and glutathione (GSH)-S-transferase by 60% in the liver. Both dyes exerted genotoxic effect as inferred from a 3-fold increase of frequency of micronucleated polychromatic erythrocytes in bone marrow, and a further increase (2-fold) was caused by ethanol liquid diet combined with Acid Green 16 treatment. Basic Orange 28 genotoxicity remained unaffected by ethanol. It is concluded that: (1) enhancement of genotoxic effect of Acid Green 16 by ethanol is caused by induction of cytochrome P-4502E1 monooxygenases resulting in an increased bioactivation of the dye; (2) lack of enhancement of the genotoxic effect of Basic Orange 28 by ethanol probably results from the dye- and ethanol-mediated stimulation of GSH-S-transferase, bypassing the cytochrome P-4502E1 bioactivation step.
authors.affiliation: Department of Toxicological Biochemistry, The Nofer Institute of Occupational Medicine, Lodz, Poland. impx@krysia.uni.lodz.pl
authors.forename: T
authors.initials: T
authors.lastname: Wrońska-Nofer
authors.forename: J
authors.initials: J
authors.lastname: Wiśniewska-Knypl
authors.forename: K
authors.initials: K
authors.lastname: Wyszyńska
authors.forename: E
authors.initials: E
authors.lastname: Dziubałtowska
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D001853:Bone Marrow / Q000187:drug effects; D004396:Coloring Agents / Q000378:metabolism / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D004912:Erythrocytes / Q000166:cytology; D000431:Ethanol / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008086:Lissamine Green Dyes / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D008862:Microsomes, Liver / Q000201:enzymology; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*
chemical_list: D001391:Azo Compounds; C108241:Basic Orange 28; D004396:Coloring Agents; D008086:Lissamine Green Dyes; D009153:Mutagens; C088063:Acid Green 16; D000431:Ethanol; D007064:L-Iditol 2-Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase