HSP70 overexpression increases resistance of V79 cells to cytotoxicity of airborne pollutants, but does not protect the mitotic spindle against damage caused by airborne toxins.
Exposure of Chinese hamster V79 cells to extracts of airborne pollutants induced formation of multipolar or incomplete mitotic spindles. To find out whether overexpression of the HSP70 chaperone protein could protect spindles against airborne toxins we constructed V79 cells stably transfected with an expression vector containing rat heat-inducible hsp70.1 gene under the control of a constitutive CMV promoter. When cells were incubated with extracts of airborne pollutants (5-20 microg/ml) no protective effect of the HSP70 protein against mitotic spindle damage was observed. Moreover, at 20 microg/ml of extracts of airborne toxins the frequency of mitotic malformations was even higher in HSP70-overexpressing cells than in control ones. Extracts of airborne pollutants of 50 microg/ml blocked the formation of mitotic figures both in control and HSP70-overexpressing cells and led to destruction of cell nuclei. However, the HSP70-overproducing cells exhibited higher survival rates when exposed to heat shock and airborne toxins than the control ones, as determined by MTT assay. This suggests that HSP70 overexpression-a frequent feature of cancer cells-should be considered as a factor facilitating survival of cells with damaged mitotic spindles and aberrantly segregated chromosomes.
Glowala
Magdalena
M
Department of Tumor Biology, Centre of Oncology - Maria Skłodowska-Curie Memorial Institute, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland.
Mazurek
Agnieszka
A
Piddubnyak
Valeria
V
Fiszer-Kierzkowska
Anna
A
Michalska
Jadwiga
J
Krawczyk
Zdzislaw
Z
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D005347:Fibroblasts; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D010957:Plasmids / Q000235:genetics; D008941:Spindle Apparatus / Q000187:drug effects* / Q000648:ultrastructure; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection
D000395:Air Pollutants, Occupational; D018840:HSP70 Heat-Shock Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue