Vinclozolin, a widely used fungizide, enhanced BaP-induced micronucleus formation in human derived hepatoma cells by increasing CYP1A1 expression.
Vinclozolin, a widely used fungicide, can be identified as a residue in numerous vegetable and fruit samples. To get insight in its genetic toxicity, we investigated the genotoxic effect of vinclozolin in the human derived hepatoma cell line HepG2 using the micronucleus (MN) assay. Additionally, to evaluate the co- or anti-mutagenic potency of vinclozolin, we treated HepG2 cells with different concentrations of vinclozolin for 24 h. Subsequently, the cells were exposed to benzo[a]pyrene (BaP) for 1h. Exposure of HepG2 cells to 50-400 microM vinclozolin alone did not cause any induction of micronuclei. However, a pronounced co-mutagenic effect was observed. MN frequencies caused by BaP increased by 30.6%, 52.8% and 65.3% after pretreatment of the cell cultures with 50, 100 and 200 microM vinclozolin, respectively. The highest concentration (400 microM) of vinclozolin tested caused cytotoxicity. Therefore, micronuclei were not considered for that concentration. To clarify the mechanism of cogenotoxicity, we assayed cytochrome P450 1A1 (CYP1A1), which plays a pivotal role in activation of BaP. Cells exposed to vinclozolin led to significant increase of CYP1A1 expression in Western blot. The result suggested that induction of CYP1A1 by vinclozolin account for its enhancing effect on genotoxicity caused by BaP.
Institute of Indoor and Environmental Toxicology, Justus-Liebig-University of Giessen, University Hospital, Aulweg 123, D-35385 Giessen, Germany.
Xin-Jiang
XJ
Wu
Wen-qing
WQ
Lu
Peter H
PH
Roos
Volker
V
Mersch-Sundermann
D001564:Benzo(a)pyrene / Q000633:toxicity*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D010080:Oxazoles / Q000633:toxicity*
D005659:Fungicides, Industrial; D009153:Mutagens; D010080:Oxazoles; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; C025643:vinclozolin