Chronic exposure to zinc chromate induces centrosome amplification and spindle assembly checkpoint bypass in human lung fibroblasts.
Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen; however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no increase in aneuploidy after a 24 h exposure to zinc chromate, but with more chronic exposures, zinc chromate induced concentration- and time-dependent increases in aneuploidy in the form of hypodiploidy, hyperdiploidy, and tetraploidy. Zinc chromate also induced centrosome amplification in a concentration- and time-dependent manner in both interphase and mitotic cells after chronic exposure, producing cells with centriolar defects. Furthermore, chronic exposure to zinc chromate induced concentration- and time-dependent increases in spindle assembly checkpoint bypass with increases in centromere spreading, premature centromere division, and premature anaphase. Last, we found that chronic exposure to zinc chromate induced a G2 arrest. All together, these data indicate that zinc chromate can induce chromosome instability after prolonged exposures.
Holmes
Amie L
AL
Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, 96 Falmouth Street, Portland, Maine 04104-9300, USA.
Wise
Sandra S
SS
Pelsue
Stephen C
SC
Aboueissa
AbouEl-Makarim
AM
Lingle
Wilma
W
Salisbury
Jeffery
J
Gallagher
Jamie
J
Wise
John Pierce
JP
D000782:Aneuploidy; D002460:Cell Line; D018385:Centrosome / Q000187:drug effects*; D002840:Chromates / Q000633:toxicity*; D043171:Chromosomal Instability / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D010316:Particle Size; D012995:Solubility; D008941:Spindle Apparatus / Q000187:drug effects*; D017967:Zinc Compounds / Q000633:toxicity*
D002840:Chromates; D017967:Zinc Compounds; C023616:zinc chromate