title: Chronic Exposure to Particulate Chromate Induces Premature Centrosome Separation and Centriole Disengagement in Human Lung Cells.
abstract: Particulate hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen. Lung tumors are characterized by structural and numerical chromosome instability. Centrosome amplification is a phenotype commonly found in solid tumors, including lung tumors, which strongly correlates with chromosome instability. Human lung cells exposed to Cr(VI) exhibit centrosome amplification but the underlying phenotypes and mechanisms remain unknown. In this study, we further characterize the phenotypes of Cr(VI)-induced centrosome abnormalities. We show that Cr(VI)-induced centrosome amplification correlates with numerical chromosome instability. We also show chronic exposure to particulate Cr(VI) induces centrosomes with supernumerary centrioles and acentriolar centrosomes in human lung cells. Moreover, chronic exposure to particulate Cr(VI) affects the timing of important centriolar events. Specifically, chronic exposure to particulate Cr(VI) causes premature centriole disengagement in S and G2 phase cells. It also induces premature centrosome separation in interphase. Altogether, our data suggest that chronic exposure to particulate Cr(VI) targets the protein linkers that hold centrioles together. These centriolar linkers are important for key events of the centrosome cycle and their premature disruption might underlie Cr(VI)-induced centrosome amplification.
authors: *Wise Laboratory of Environmental and Genetic Toxicology and Department of Applied Medical Sciences, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104; and.
authors: Julieta
authors: J
authors: Martino
authors: *Wise Laboratory of Environmental and Genetic Toxicology and Department of Applied Medical Sciences, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104; and.
authors: Amie L
authors: AL
authors: Holmes
authors: *Wise Laboratory of Environmental and Genetic Toxicology and Department of Applied Medical Sciences, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104; and.
authors: Hong
authors: H
authors: Xie
authors: *Wise Laboratory of Environmental and Genetic Toxicology and Department of Applied Medical Sciences, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104; and Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40068.
authors: Sandra S
authors: SS
authors: Wise
authors: *Wise Laboratory of Environmental and Genetic Toxicology and Department of Applied Medical Sciences, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104; and Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40068 john.wise@louisville.edu.
authors: John Pierce
authors: JP
authors: Wise
mesh_terms: D002460:Cell Line; D002502:Centrioles / Q000187:drug effects*; D018385:Centrosome / Q000187:drug effects*; D002840:Chromates / Q000008:administration & dosage / Q000633:toxicity; D002857:Chromium / Q000008:administration & dosage / Q000633:toxicity*; D043171:Chromosomal Instability / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity*; D017967:Zinc Compounds / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D002840:Chromates; D052638:Particulate Matter; D017967:Zinc Compounds; C023616:zinc chromate; D002857:Chromium; C074702:chromium hexavalent ion
keywords: CIN; centriole disengagement; centrosome amplification; centrosome separation; chromium