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2,4-Diaminotoluene (2,4-DAT)-induced DNA damage, DNA repair and micronucleus formation in the human hepatoma cell line HepG2.

Abstract
2,4-Diaminotoluene (2,4-DAT) is a widely used industrial intermediate and human exposure is possible in the dye and plastics industries. We investigated the genotoxicity of the environmental pollutant, 2,4-DAT, in human HepG2 cells using the unscheduled DNA synthesis (UDS) test, the micronucleus (MN) assay and single-cell gel electrophoresis (SCGE). 2,4-DAT was first tested by the RNA synthesis inhibition test as a cytotoxicity assay: the IC(50) of 2,4-DAT was 5.2 mM after 20 h of exposure. The compound had a genotoxic effect at concentrations from 1.45 to 6.80 mM in both micronucleus and comet assays. In the micronucleus assay, the number of MN/1000 BNC was 3.5 times higher at a concentration of 6.80 mM 2,4-DAT than in the negative control. At the same concentration, DNA migration (SCGE) showed an Olive tail moment (OTM) of 3.56+/-0.45, as compared to 0.19+/-0.02 for the negative control. The UDS test detected genotoxic effects at lower concentrations than did the other assays (0.01-5 mM). The percentage of cells in repair increased in a concentration-dependent manner to a maximum of 57% at 1mM. At the highest concentration tested (5 mM), the NNG/cell score was 13.6+/-0.5 whereas it was -2.7+/-0.5 for the negative control. These data, based on various endpoints, show a midly genotoxic effect of 2,4-DAT in the HepG2 cells and confirm that this cell line is a suitable model to study the toxic effects of aromatic amines.
AuthorsIsabelle Séverin, Adeline Jondeau, Laurence Dahbi, Marie-Christine Chagnon
JournalToxicology (Toxicology) Vol. 213 Issue 1-2 Pg. 138-46 (Sep 15 2005) ISSN: 0300-483X [Print] Ireland
PMID15996806 (Publication Type: Journal Article)
Chemical References
  • Carcinogens
  • Phenylenediamines
  • 2,4-diaminotoluene
  • Uridine
Topics
  • Carcinogens (toxicity)
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Comet Assay
  • DNA Damage
  • DNA Repair
  • Dose-Response Relationship, Drug
  • Humans
  • Liver Neoplasms
  • Micronucleus Tests
  • Phenylenediamines (toxicity)
  • Uridine (metabolism)

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