title: Urine from current smokers induces centrosome aberrations and spindle defects in vitro in nonmalignant human cell lines.
abstract: Tobacco smoke containing numerous derived chemical carcinogens is the main risk factor for urothelial carcinoma. These carcinogens can induce DNA damage leading to chromosomal instability, which plays a fundamental role in urothelial carcinogenesis. Possible mechanisms could be centrosomal aberrations, which cause defective spindles and may be responsible for genetic instability. We evaluated the effect of urine from never smokers (NS) and current smokers (CS) in concentrations of 0 to 50% on cell proliferation, chromosomes, centrosomes, and the spindle status of normal human dermal fibroblasts and normal human urothelial cells (UROtsa). After 2 weeks of urine treatment, cell cultures were analyzed by centrosome and spindle immunostaining and conventional cytogenetics. Effects were compared to results of untreated controls. Analysis of normal human dermal fibroblasts and UROtsa cells revealed that urine from CS induced higher values of centrosome aberrations in a dose-dependent and cell line-independent manner when compared to cultures treated with urine from NS and untreated controls. Centrosomal alterations correlated with spindle defects and an increase of sporadic chromosomal aberrations. The observations suggest a causative role of chemical carcinogens in urine from CS in the origin of centrosome and spindle defects in vitro leading to chromosomal instability and may be involved in urothelial carcinogenesis.
authors.affiliation: Abteilung für Urologie, Medizinische Fakultät Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Gabriel
authors.forename: Michelle
authors.initials: M
authors.lastname: Giehl
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Haass
authors.forename: Lutz
authors.initials: L
authors.lastname: Trojan
authors.forename: Maurice Stephan
authors.initials: MS
authors.lastname: Michel
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seifarth
authors.forename: Alice
authors.initials: A
authors.lastname: Fabarius
mesh_terms: D000328:Adult; D002273:Carcinogens; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D018385:Centrosome / Q000648:ultrastructure*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D012867:Skin / Q000166:cytology; D012907:Smoking; D008941:Spindle Apparatus; D019459:Urothelium / Q000166:cytology
chemical_list: D002273:Carcinogens