Effect of copper on the cytotoxicity of phenanthrene and 9,10-phenanthrenequinone to the human placental cell line, JEG-3.
The trophoblast cell line, JEG-3, was used to study the cytotoxicity of phenanthrene, 9,10-phenanthrenequinone (PHEQ), anthracene, and 9,10-anthracenedione alone and with copper. The endpoints were the capacity of cultures to reduce alamar Blue (AB), a measure of energy metabolism, and to convert carboxyfluorescein diacetate acetoxymethyl ester (CFDA AM) to carboxyfluorescein, an indication of membrane integrity. Only PHEQ elicited a cytotoxic response. PHEQ caused a concentration-dependent decline in AB but not in CFDA AM readings, suggesting an impairment to energy metabolism. In the presence of copper, PHEQ concentration-response curves were shifted to the left for AB and were obtained with CFDA AM. The Cu/PHEQ synergy is attributed to an increase in redox cycling and production of reactive oxygen species (ROS), which overwhelm antioxidant defenses, damaging energy metabolism first and then membrane integrity. The impermeable copper chelator, bathocuproine, reduced the PHEQ/copper interaction, but the permeable chelator, neocuproine, and copper together were cytotoxic.
Peters
Zachary J
ZJ
Department of Biology, University of Waterloo, 200 University Ave. W., Waterloo, Ontario N2L 3G1, Canada.
Nykamp
Julie A
JA
Passaperuma
Kavitha
K
Carlson
John C
JC
DeWitte-Orr
Stephanie J
SJ
Greenberg
Bruce M
BM
Bols
Niels C
NC
D000873:Anthracenes / Q000633:toxicity; D000880:Anthraquinones / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000633:toxicity; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010616:Phenanthrenes / Q000633:toxicity*; D010618:Phenanthrolines / Q000633:toxicity; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000873:Anthracenes; D000880:Anthraquinones; D002614:Chelating Agents; D004785:Environmental Pollutants; D010616:Phenanthrenes; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; C042834:9,10-anthraquinone; C005399:9,10-phenanthrenequinone; C031181:phenanthrene; D003300:Copper; C002701:neocuproine; C002478:bathocuproine; C034020:anthracene; C029892:cupric chloride