title: Is the natural PCDD/PCDF mixture toxic for human placental JEG-3 cell line? The action of the toxicants on hormonal profile, CYP1A1 activity, DNA damage and cell apoptosis.
abstract: 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.
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-306 Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Augustowska
authors.forename: Zofia
authors.initials: Z
authors.lastname: Magnowska
authors.forename: Maria
authors.initials: M
authors.lastname: Kapiszewska
authors.forename: Ewa L
authors.initials: EL
authors.lastname: Gregoraszczuk
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000302:isolation & purification / Q000633:toxicity*; D002244:Carbon / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D060729:Coal Ash; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D018736:DNA Adducts; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D000072338:Dibenzofurans, Polychlorinated; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000633:toxicity*; D011374:Progesterone / Q000378:metabolism; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D001572:Benzofurans; D006063:Chorionic Gonadotropin; D060729:Coal Ash; D018736:DNA Adducts; D000072338:Dibenzofurans, Polychlorinated; D004785:Environmental Pollutants; D052638:Particulate Matter; D000072317:Polychlorinated Dibenzodioxins; D011374:Progesterone; D002244:Carbon; D019363:Cytochrome P-450 CYP1A1