title: Clastogenic but not apoptotic effects on human artery endothelial cells by concentrations of inorganic lead inhibiting their nitric oxide production.
abstract: Human coronary artery endothelial cells (HCAEC 5156) were cultured as monolayers and exposed to concentrations of lead (as acetate, Pb) in the culture medium similar or lower than those commonly found in the blood of human beings occupationally or environmentally exposed to this element. Only at the concentration of 200 ng/mL, Pb reduced growth rate of HCAEC 5156 cells starting from the 3rd day and up too the 5th day of incubation. On the other hand, Pb (0.2, 2 and 200 ng/mL) increased concentration-dependently micronuclei formation in binucleated HCAEC 5156 cells, as it was shown by the cytokinesis-blocked micronucleus assay (CMBN assay) carried out after 48 hours of exposure to the metal. However Pb was unable, at all the above concentrations to induce apoptosis in the HCAEC 5156 cells following a 48 hour-exposure, as shown by an electorphoretic apoptotic DNA fragmentation test. Moreover, Pb (2 and 200 ng/mL) reduced significantly the concentration of nitric oxide (NO, determined analytically as L-citrulline) in both culture medium and cytosol of HCAEC 5156 cells following a 7 day-exposure to the element. Results were discussed also in relation so evidences of other studies reporting genotoxic and/or apoptotic effects of Pb on various cell types at very elevated dosages of concentrations. The observed clastogenic effects of Pb were explained through a series of mechanisms involving interactions between oxygen reactive species and NO and/or reduced NO synthesis in the endothelium, thus leading to a depressed NO bioavailability. This research first shows that Pb is provided with clastogenic but not apoptotic effects on cultured human endothelial cells. It was emphasized that such effects are induced by Pb concentrations similar to those commonly found in blood and tissues of laboratory animals showing Pb induced cardiovascular and/or neuropsychological alterations.
authors.affiliation: Section of Pharmacology and Toxicology, Department of Basic and Applied Biology, University of L'Aquila, Coppito, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Carmignani
authors.forename: M
authors.initials: M
authors.lastname: Felaco
authors.forename: P
authors.initials: P
authors.lastname: Boscolo
authors.forename: M
authors.initials: M
authors.lastname: Di Gioacchino
authors.forename: L
authors.initials: L
authors.lastname: Di Giampaolo
authors.forename: Q
authors.initials: Q
authors.lastname: Niu
authors.forename: P
authors.initials: P
authors.lastname: Cesare
authors.forename: A R
authors.initials: AR
authors.lastname: Volpe
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007855:Lead Poisoning / Q000378:metabolism / Q000473:pathology; D009153:Mutagens / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D009942:Organometallic Compounds / Q000494:pharmacology*
chemical_list: D017077:Culture Media, Conditioned; D009153:Mutagens; D009942:Organometallic Compounds; D009569:Nitric Oxide; C008261:lead acetate