title: Micronucleus assay with urine derived cells (UDC): a review of its application in human studies investigating genotoxin exposure and bladder cancer risk.
abstract: The first micronucleus (MN) study with urine derived cells (UDC) appeared 30 years ago. So far, 56 investigations have been published with this method and it was shown that it can be used for the detection of chromosomal damage caused by environmental and lifestyle factors as well as by occupational exposures and certain diseases This approach may be also useful as a diagnostic tool for the detection and prognosis of bladder cancer. The test system has been improved in the last years, i.e., it was shown that, apart from MN also other nuclear anomalies can be evaluated in UDC which are found in other types of epithelial cells as well (e.g., in oral and nasal cells) and are indicative for acute toxicity (pyknosis, karyorrhexis, karyolysis, condensed chromatin) and genomic instability (nuclear buds, binucleates). Furthermore, an improved protocol with Carnoy I fixation and Papanicolaou stain was developed which enables the discrimination between cells which originate from the cervix and those from the urothelium. The evaluation of the currently available results indicates that exposures and health conditions which are associated with increased cancer rates in the bladder (and possibly also in other organs) lead to positive results in MN-UDC assays and a limited number of studies indicate that this method may be equally sensitive as other more frequently used human biomonitoring assays. The major shortcoming of the UDC-MN method is the lack of standardization; the evaluation of the current data shows that a variety of staining and fixation methods are used and that the numbers of evaluated cells vary over a broad range. These inconsistencies may account for the large inter-laboratory variations of the background frequencies. In order to improve the reliability of the method, further standardization and validation is required. Therefore an international program should be initiated in which a similar strategy could be used as in previous validation/standardization projects concerning MN-cytome assays with lymphocytes and buccal cells.
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Armen
authors.initials: A
authors.lastname: Nersesyan
authors.affiliation: Institute of Environmental Health, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.affiliation: CSIRO Preventative Health Flagship, PO Box 10041, Adelaide BC 5000, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
authors.affiliation: Unit of Environmental Carcinogenesis, IRCCS AUO San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bolognesi
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Misik
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Wultsch
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21/7, A-8010 Graz, Austria.
authors.forename: Michaele
authors.initials: M
authors.lastname: Hartmann
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. Electronic address: siegfried.knasmueller@meduniwien.ac.at.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmueller
mesh_terms: D002477:Cells; D002584:Cervix Uteri / Q000166:cytology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D015162:Micronucleus Tests / Q000379:methods / Q000639:trends; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology; D019459:Urothelium / Q000166:cytology*
keywords: Cancer risks; Exposure; Micronucleus; Urine derived cells; Urothelial cells