Augustowska Katarzyna, Magnowska Zofia, Kapiszewska Maria, Gregoraszczuk Ewa L
Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-306 Krakow, Poland.
Hum Exp Toxicol. 2007 May;26(5):407-17. doi: 10.1177/0960327107073119.
The present study was conducted to define the action of a mixture obtained by the extraction and purification of real fly ash, on specific toxicity endpoints, such as hormonal secretion, CYP1A1 expression, DNA damage and cell apoptosis. JEG-3 cell line was exposed in vitro to different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or Polychlorinated dibenzo-p-dioxin/Polychlorinated dibenzo-P-furan (PCDD/PCDF) mixture. Both TCDD and the mixture decreased hCG secretion, while inhibition of progesterone levels was noted only under the influence of TCDD. The changes in hormone production were not due to the action on cell viability. There were time-dependent differences in CYP1A1 expression in cells exposed to TCDD and PCDD/PCDF mixture. Both TCDD and PCDD/PCDF mixture did not induce the DNA damage, as evaluated by the comet assay. Significantly lower DNA migration from the head of comet into the comet tail was noted after the removal of reagents. The highest efficiency of this process was noted 4 h after the TCDD and 24 h after the PCDD/PCDF mixture removal. These results suggest that the DNA adducts and/or DNA-DNA cross-links were formed. Neither TCDD nor PCDD/PCDF mixture had any effect on cell apoptosis assessed by caspase-3 activity and Hoechst 33258. Taken together, these findings clearly indicate a weaker action of the mixture when compared with TCDD. However, in both cases, their action was not due to the induction of the DNA damage and subsequent cell apoptosis but due to a direct influence of these toxicants on placental hormone production.
本研究旨在确定通过提取和纯化实际飞灰获得的混合物对特定毒性终点的作用，如激素分泌、CYP1A1表达、DNA损伤和细胞凋亡。JEG-3细胞系在体外暴露于不同剂量的2,3,7,8-四氯二苯并对二恶英（TCDD）或多氯二苯并对二恶英/多氯二苯并呋喃（PCDD/PCDF）混合物。TCDD和该混合物均降低了hCG分泌，而仅在TCDD的影响下才观察到孕酮水平的抑制。激素产生的变化并非由于对细胞活力的作用。暴露于TCDD和PCDD/PCDF混合物的细胞中CYP1A1表达存在时间依赖性差异。通过彗星试验评估，TCDD和PCDD/PCDF混合物均未诱导DNA损伤。去除试剂后，观察到彗星头部向彗尾的DNA迁移明显降低。在去除TCDD后4小时和去除PCDD/PCDF混合物后24小时观察到该过程的最高效率。这些结果表明形成了DNA加合物和/或DNA-DNA交联。TCDD和PCDD/PCDF混合物对通过caspase-3活性和Hoechst 33258评估的细胞凋亡均无任何影响。综上所述，这些发现清楚地表明与TCDD相比，该混合物的作用较弱。然而，在这两种情况下，它们的作用并非由于诱导DNA损伤和随后的细胞凋亡，而是由于这些毒物对胎盘激素产生的直接影响。
