title: The cytotoxicity and genotoxicity of particulate and soluble hexavalent chromium in human lung cells.
abstract: Hexavalent chromium (Cr(VI)) is a human lung carcinogen. Cr(VI) is a particularly important and dangerous carcinogen, because there is widespread exposure to it both occupationally and to the general public. However, despite the potential for widespread exposure and the fact that the lung is its target organ, there are few reports of the genotoxicity of Cr(VI) in human lung cells. Clearly, in order to better understand this carcinogen, its effects in its target cells need to be evaluated. Accordingly, we determined the cytotoxicity and clastogenicity of both particulate (water-insoluble) and soluble Cr(VI) in primary human bronchial fibroblasts (PHBFs). We used lead chromate (PbCrO(4)) and sodium chromate (Na(2)CrO(4)) as prototypical particulate and soluble Cr(VI) salts, respectively. Both compounds induced concentration-dependent cytotoxicity after a 24h exposure in PHBFs. The relative survival was 87, 46, 26 and 2% after exposure to 0.1, 0.5, 1 and 5 microg/cm(2) PbCrO(4), respectively, and 74, 57, 13 and 0% after exposure to 1, 2.5, 5 and 10 microM Na(2)CrO(4), respectively. Similarly, the amount of chromosome damage increased with concentration after 24h exposure to both compounds. Specifically, 0.1, 0.5 and 1 microg/cm(2) PbCrO(4) damaged 15, 34 and 42% of metaphase cells with the total amount of damage reaching 18, 40 and 66 aberrations per 100 metaphases, respectively. PbCrO(4) (5 microg/cm(2)) induced such profound cell cycle delay that no metaphases were found. Na(2)CrO(4) (1 and 2.5 microM) damaged 18 and 33% of metaphase cells with the total amount of damage reaching 19 and 43 aberrations per 100 metaphases, respectively. Na(2)CrO(4) (5 and 10 microM) induced such profound cell cycle delay that no metaphases were found. Overall the data clearly indicate that Cr(VI) compounds are cytotoxic and genotoxic to human lung cells.
authors.affiliation: Laboratory of Environmental and Genetic Toxicology, Department of Epidemiology and Public Health, Division of Environmental Health Sciences, Yale University, School of Medicine, P.O. Box 208034, New Haven, CT 06520-8034, USA. john.wise@yale.edu
authors.forename: John Pierce
authors.initials: JP
authors.lastname: Wise
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Wise
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Little
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002840:Chromates / Q000633:toxicity; D002857:Chromium / Q000633:toxicity*; D002869:Chromosome Aberrations; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007854:Lead / Q000633:toxicity; D008168:Lung / Q000166:cytology* / Q000187:drug effects*; D009153:Mutagens; D017670:Sodium Compounds / Q000633:toxicity; D013997:Time Factors
chemical_list: D002840:Chromates; D009153:Mutagens; D017670:Sodium Compounds; D002857:Chromium; D007854:Lead; C028982:sodium chromate(VI); D004247:DNA; C031895:lead chromate