title: Differences in the action of lower and higher chlorinated polychlorinated naphthalene (PCN) congeners on estrogen dependent breast cancer cell line viability and apoptosis, and its correlation with Ahr and CYP1A1 expression.
abstract: There are data showing that exposition to PCNs mixture increased incidence of gastrointestinal and respiratory neoplasms, but data regarding incidence of hormone-dependent cancer so far not shown. The objective was to determine if exposure to single lower and higher chlorinated PCN congeners is associated with altered proliferation and apoptosis of estrogen dependent breast cancer cells, and whether such effects are related to induction of AhR and CYP1A1 protein expression. MCF-7 cells were exposed to PCN 34, 39, 42, 46, 48, 52, 53, 54, 66, 67, 70, 71, 73 and 74 at concentrations of 100-10,000pg/ml. We evaluated the action of these PCN congeners on cell proliferation, DNA fragmentation and caspase-8,-9 activity. AhR and CYP1A1 protein expression and CYP1A1 activity was evaluated at a concentration of 1000pg/ml. An opposite action of tri- to tetraCNs than of penta-to heptaCNs on cell proliferation and apoptosis was evident. Tetra PCNs increased cell proliferation, but had no effect on DNA fragmentation nor caspase activity. Fast induction of CYP1A1 protein expression under the influence of lower chlorinated PCNs suggests faster metabolism and a possible stimulatory action of locally formed metabolites on cell proliferation. None of the higher chlorinated PCNs affected cell proliferation but all higher chlorinated PCNs increased caspase-8 activity, and hexa PCNs also increased caspase-9 activity. The rapid activation of the Ah receptor and CYP1A1 protein expression by higher chlorinated PCNs point to their toxicity; however, it is not sufficient for potential carcinogenicity. Action of lower chlorinated naphthalenes metabolites should be explored.
authors: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University in Krakow, Gronostajowa 9, 30-387 Kraków, Poland.
authors: Ewa L
authors: EL
authors: Gregoraszczuk
authors: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University in Krakow, Gronostajowa 9, 30-387 Kraków, Poland.
authors: Justyna
authors: J
authors: Barć
authors: Research Group of Environmental Chemistry, Ecotoxicology & Food Toxicology, Institute of Environmental Sciences & Public Health, University of Gdansk, Sobieskiego 18, 80-952 Gdansk, Poland. Electronic address: ewa.gregoraszczuk@uj.edu.pl.
authors: Jerzy
authors: J
authors: Falandysz
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009281:Naphthalenes / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
chemical_list: D004967:Estrogens; D009281:Naphthalenes; D018336:Receptors, Aryl Hydrocarbon; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9
keywords: AhR; Apoptosis; CYP 1A1; MCF-7 breast cancer cell; PCN; Proliferation