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Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation

  • Genotoxicity
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An Erratum to this article was published on 19 May 2005


Particle-induced carcinogenicity is not well understood, but might involve inflammation. The proinflammatory cytokine tumor necrosis factor (TNF) is considered to be an important mediator in inflammation. We investigated its role in particle-induced inflammation and DNA damage in mice with and without TNF signaling. TNF−/− mice and TNF+/+ mice were exposed by inhalation to 20 mg m−3 carbon black (CB), 20 mg m−3 diesel exhaust particles (DEP), or filtered air for 90 min on each of four consecutive days. DEP, but not CB particles, induced infiltration of neutrophilic granulocutes into the lung lining fluid (by the cellular fraction in the bronchoalveolar lavage fluid), and both particle types induced interleukin-6 mRNA in the lung tissue. Surprisingly, TNF−/− mice were intact in these inflammatory responses. There were more DNA strand breaks in the BAL cells of DEP-exposed TNF−/− mice and CB-exposed mice compared with the air-exposed mice. Thus, the CB-induced DNA damage in BAL-cells was independent of neutrophil infiltration. The data indicate that an inflammatory response was not a prerequisite for DNA damage, and TNF was not required for the induction of inflammation by DEP and CB particles.

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This work was supported by grant no. 2052-03-0016 from the Danish Research Council, by grant no. 9801314 from the Danish Medical Research Council, by the Danish Ministry of Interior and Health, Research Centre for Environmental Health and a scholarship to Anne Thoustrup Saber from the Danish Research Academy. The technical assistance from Gitte B. Kristiansen and Lourdes M. Pedersen is gratefully acknowledged. The authors thank Lesley Probert, Hellenic Pasteur Institute, Athens for the permission to use the TNF−/− mice. The experiments were approved by the Danish “Animal Experimentation Inspectorate”.

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Correspondence to Håkan Wallin.

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Saber, A.T., Bornholdt, J., Dybdahl, M. et al. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation. Arch Toxicol 79, 177–182 (2005).

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