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Induction of CYP1A1 in rat lung cells following in vivo and in vitro exposure to quartz

  • Organ Toxicity and Mechanisms
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Abstract

Respirable quartz has been classified as a human lung carcinogen, but the mechanism by which quartz exposure leads to lung cancer has not been clarified. Consistently higher risks of lung cancer are reported in smokers with quartz exposure and we therefore hypothesised that quartz exposure may alter the expression of enzyme systems involved in activation/detoxification of pre-carcinogens in cigarette smoke. More specifically we studied cytochrome P4501A1 (CYP1A1) expression using reverse transcriptase polymerase chain reaction and immunohistochemistry (IHC) upon in vitro and in vivo quartz exposure. In vitro incubation of rat lung epithelial cells with DQ12 quartz for 24 h showed a dose-dependent induction of CYP1A1-mRNA. On the other hand, CYP1A1 message was not increased in lung epithelial cells isolated from rats at 3, 28 or 90 days after intratracheal instillation of 2 mg DQ12. Following IHC for CYP1A1 protein in rat lung sections from later time-points (180 and 360 days), we observed an increase in the number of CYP1A1 positive cells. After in vivo quartz exposure, protein expression of the Aryl hydrocarbon receptor (AhR) was increased and nuclear translocation of AhR was observed at the same time-points. In conclusion, our findings demonstrate an effect of quartz exposure on chronic CYP1A1 expression in vivo, whereas the in vitro models show an immediate upregulation. We suggest that this upregulation of CYP1A1 may act as a co-carcinogenic pathway in quartz exposed workers by activation of pre-carcinogens such as those present in cigarette smoke.

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Acknowledgements

We acknowledge the support of Silikose-Gesellschaft and Ministerium für Wirtschaft, Mittelstand, Technologie und Verkehr Nordrhein Westfalen (Germany). The authors thank Dr. Klaus Unfried for his help with the instillation of the animals. We thank Mrs. Astrid Winzer, Christel Weishaupt and Veena Suri for their technical support in this extensive animal study. The authors thank Mr. E. Jermann and Mrs. A. Chiarotti, Analytical Chemistry, Medical Institute for Environmental Hygiene Düsseldorf, Germany, for the quartz preparation to determine the PAH content as well as correlation of PAH values. Mr. Edwin Moonen from the Department of Health Risk Analysis and Toxicology, University Maastricht, is acknowledged for analysis of PAH-levels in extracted DQ12 preparations. The authors thank Dr. Rodger Duffin for his linguistic assistance in finishing the manuscript. We declare that all animal experiments comply with the current laws of Germany.

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Authors and Affiliations

  1. Particle Research, Institut für Umweltmedizinische Forschung (IUF) gGmbH an der Heinrich-Heine Universität, Dusseldorf, Germany

    Andrea Becker, Catrin Albrecht, Roel P. F. Schins, Doris Höhr & Kirstin Ledermann

  2. Department of Health Risk Analysis and Toxicology, University of Maastricht, Maastricht, The Netherlands

    Ad M. Knaapen

  3. Centre of Expertise in Life Sciences, Zuyd University, Po Box 550, 6400 AN, Heerlen, The Netherlands

    Paul J. A. Borm

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  1. Andrea Becker
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Correspondence to Paul J. A. Borm.

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Becker, A., Albrecht, C., Knaapen, A.M. et al. Induction of CYP1A1 in rat lung cells following in vivo and in vitro exposure to quartz. Arch Toxicol 80, 258–268 (2006). https://doi.org/10.1007/s00204-006-0084-2

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  • DOI: https://doi.org/10.1007/s00204-006-0084-2

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