Genotoxicity of industrial dyes under the inductive effect of ethanol on monooxygenase system in mice

Mutat Res. 1997 Aug 14;392(3):229-35. doi: 10.1016/s1383-5718(97)00067-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azo Compounds / metabolism
  • Azo Compounds / toxicity*
  • Biotransformation
  • Bone Marrow / drug effects
  • Coloring Agents / metabolism
  • Coloring Agents / toxicity*
  • Cytochrome P-450 CYP2E1 / biosynthesis
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Enzyme Induction
  • Erythrocytes / cytology
  • Ethanol / pharmacology*
  • Glutathione Transferase / metabolism
  • L-Iditol 2-Dehydrogenase / blood
  • Lissamine Green Dyes / metabolism
  • Lissamine Green Dyes / toxicity*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Micronucleus Tests
  • Microsomes, Liver / enzymology
  • Mutagens / metabolism
  • Mutagens / toxicity*

Substances

  • Azo Compounds
  • Basic Orange 28
  • Coloring Agents
  • Lissamine Green Dyes
  • Mutagens
  • Acid Green 16
  • Ethanol
  • L-Iditol 2-Dehydrogenase
  • Cytochrome P-450 CYP2E1
  • Glutathione Transferase