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On the mechanism of Cr (VI)-induced carcinogenesis: Dose dependence of uptake and cellular responses

  • Chapter
Molecular Mechanisms of Metal Toxicity and Carcinogenesis

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 34))

Abstract

Cr (VI) compounds are widely used industrial chemicals and are recognized human carcinogens. The mechanisms of carcinogenesis associated with these compounds remain to be investigated. The present study focused on dose-dependence of Cr (VI)-induced uptake and cellular responses. The results show that Cr (VI) is able to enter the cells (human lung epithelial cell line A549) at low concentration (< 10 ltM) and that the Cr (VI) uptake appears to be a combination of saturable transport and passive diffusion. Electron spin resonance (ESR) trapping measurements showed that upon stimulation with Cr (VI), A549 cells were able to generate reactive oxygen species (ROS). The amount of ROS generated depended on the Cr (VI) concentration. ROS generation involved NADPH-dependent flavoenzymes. Cr (VI) affected the following cellular parameters in a dose-dependent manner, (a) activation of nuclear transcription factors NF-KB, and p53, (b) DNA damage, (c) induction of cell apoptosis, and (d) inhibition of cell proliferation. The activation of transcription factors was assessed by electrophoretic mobility shift assay and western blot analysis, DNA damage by single cell gel electrophoresis assay, cell apoptosis by DNA fragmentation assay, and cell proliferation by a non-radioactive ELISA kit. At the concentration range used in the present study, no thresholds were found in all of these cell responses to Cr (V I). The results may guide further research to better understand and evaluate the risk of Cr (VI)-induced carcinogenesis at low levels of exposure. (Mol Cell Biochem 222: 221 229, 2001)

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Author information

Authors and Affiliations

  1. College of Pharmacy, USA

    Kejian Liu

  2. Department of Earth and Planetary Sciences, University of New Mexico, Albuquerque, NM

    John Husler

  3. Pathology and 3Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WT, USA

    Jianping Ye, Stephen S. Leonard, Debbie Cutler, Fei Chen, Suwei Wang, Zhuo Zhang, Min Ding, Liying Wang & Xianglin Shi

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  1. Kejian Liu
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  2. John Husler
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  3. Jianping Ye
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  4. Stephen S. Leonard
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  5. Debbie Cutler
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  6. Fei Chen
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  7. Suwei Wang
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  8. Zhuo Zhang
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  9. Min Ding
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  10. Liying Wang
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  11. Xianglin Shi
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Editor information

Editors and Affiliations

  1. Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, 26505, Morgantown, WV, USA

    Xianglin Shi , Vince Castranova  & Val Vallyathan ,  & 

  2. Occupational Safety and Health Administration, Washington DC, USA

    William G. Perry

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© 2001 Springer Science+Business Media New York

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Liu, K. et al. (2001). On the mechanism of Cr (VI)-induced carcinogenesis: Dose dependence of uptake and cellular responses. In: Shi, X., Castranova, V., Vallyathan, V., Perry, W.G. (eds) Molecular Mechanisms of Metal Toxicity and Carcinogenesis. Developments in Molecular and Cellular Biochemistry, vol 34. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0793-2_26

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  • DOI: https://doi.org/10.1007/978-1-4615-0793-2_26

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5242-6

  • Online ISBN: 978-1-4615-0793-2

  • eBook Packages: Springer Book Archive

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