title: Results of micronucleus assays with individuals who are occupationally and environmentally exposed to mercury, lead and cadmium.
abstract: Millions of humans are exposed occupationally and environmentally to lead, mercury and cadmium compounds. Mercury compounds are less abundant but some of them belong to the most toxic chemicals which are known. We evaluated the literature to find out if these metals act in humans as genotoxic carcinogens and if their health effects can be predicted by use of micronucleus (MN) assays with lymphocytes and/or with other genotoxicity tests. Numerous studies showed that lead and mercury induce cancer in humans and also in animals, in vitro experiments with cultured cells indicate that they cause DNA damage via different molecular mechanisms including release of reactive oxygen species and interactions with DNA repair processes. Also in most human studies, positive results were obtained in MN tests with lymphocytes (all 15 occupational studies with lead yielded positive results, with mercury 6 out of 7 investigations were positive). For cadmium, there is clear evidence that it causes cancer in humans; however, induction of chromosomal damage was only seen in high dose experiments with mammalian cells while results of animal and human studies yielded conflicting results (only in 2 of 5MN trials with humans positive findings were reported). Possibly, non-genotoxic mechanisms such as inhibition of apoptosis and interaction with signaling pathways account for the carcinogenic properties of cadmium species. The findings of MN studies with lead and mercury are in excellent agreement with results which were obtained with other endpoints (e.g. chromosomal aberrations and comet formations) and it is evident that this approach can be used for occupational and environmental monitoring of exposed individuals. Important future tasks will be the realization of larger studies with a uniform standardized protocol, the additional evaluation of anomalies other than MN (nuclear buds and bridges) and the combination of such trials with investigations which allow to define the molecular mechanisms relevant for exposed humans.
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
authors.forename: Armen
authors.initials: A
authors.lastname: Nersesyan
authors.affiliation: Institute of Environmental Health, Center for Public Health, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Waldherr
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Setayesh
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria. Electronic address: miroslav.misik@meduniwien.ac.at.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Mišík
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Wultsch
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia.
authors.forename: Metka
authors.initials: M
authors.lastname: Filipic
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Gustavo Rafael
authors.initials: GR
authors.lastname: Mazzaron Barcelos
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria. Electronic address: siegfried.knasmueller@meduniwien.ac.at.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmueller
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004781:Environmental Exposure; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008628:Mercury / Q000633:toxicity*; D015162:Micronucleus Tests / Q000379:methods*; D016273:Occupational Exposure
chemical_list: D002104:Cadmium; D007854:Lead; D008628:Mercury
keywords: Cadmium; Cytokinesis-block micronucleus assay; Lead; Lymphocytes; Mercury; Occupational exposure