title: Cytoplasmic p21(CIP1/WAF1), ERK1/2 activation, and cytoskeletal remodeling are associated with the senescence-like phenotype after airborne particulate matter (PM(10)) exposure in lung cells.
abstract: The exposure to particulate matter with a mean aerodynamic diameter ≤10 μm (PM10) from urban zones is considered to be a risk factor in the development of cancer. The aim of this work was to determine if PM10 exposure induces factors related to the acquisition of a neoplastic phenotype, such as cytoskeletal remodeling, changes in the subcellular localization of p21(CIP1/WAF1), an increase in β-galactosidase activity and changes in cell cycle. To test our hypothesis, PM10 from an industrial zone (IZ) and a commercial zone (CZ) were collected, and human adenocarcinoma lung cell cultures (A549) were exposed to a sublethal PM10 concentration (10 μg/cm(2)) for 24 h and 48 h. The results showed that PM10 exposure induced an increase in F-actin stress fibers and caused the cytoplasmic stabilization of p21(CIP1/WAF1) via phosphorylation at Thr(145) and Ser(146) and the phosphorylation of ERK1/2 on Thr(202). Changes in the cell cycle or apoptosis were not observed, but an increase in β-galactosidase activity was detected. The PM10 from CZ caused more dramatic effects in lung cells. We conclude that PM10 exposure induced cytoplasmic p21(CIP1/WAF1) retention, ERK1/2 activation, cytoskeleton remodeling and the acquisition of a senescence-like phenotype in lung cells. These alterations could have mechanistic implications regarding the carcinogenic potential of PM10.
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 México, D.F., Mexico.
authors.forename: Yesennia
authors.initials: Y
authors.lastname: Sánchez-Pérez
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Iztacala, CP 54090 Tlalnepantla, Estado de México, Mexico.
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Chirino
authors.affiliation: Department of Pediatrics, University of Alberta, 1048 RTF, 8308 114St Edmonton, Edmonton, AB T6G 2V2, Canada.
authors.forename: Álvaro Román
authors.initials: ÁR
authors.lastname: Osornio-Vargas
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, INCan; Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico, Mexico.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Herrera
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 México, D.F., Mexico.
authors.forename: Rocío
authors.initials: R
authors.lastname: Morales-Bárcenas
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 México, D.F., Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Saavedra
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 México, D.F., Mexico.
authors.forename: Imelda
authors.initials: I
authors.lastname: González-Ramírez
authors.affiliation: Instituto de Física, Universidad Nacional Autónoma de México, A.P. 20-364, 01000 Mexico, D.F., Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Miranda
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 México, D.F., Mexico. Electronic address: claudia.garciac@salud.gob.mx.
authors.forename: Claudia María
authors.initials: CM
authors.lastname: García-Cuellar
mesh_terms: D000199:Actins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology; D003599:Cytoskeleton / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D010641:Phenotype; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D022502:Stress Fibers / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000199:Actins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D052638:Particulate Matter; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D001616:beta-Galactosidase
keywords: Cytoskeleton remodeling; PM(10); Particulate matter; Senescence-like; p21(CIP1/WAF1) cytoplasmic