Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation.
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.
Saber
Anne T
AT
National Institute of Occupational Health, Lersø Parkallé 105, 2100, Copenhagen, Denmark.
Bornholdt
Jette
J
Dybdahl
Marianne
M
Sharma
Anoop K
AK
Loft
Steffen
S
Vogel
Ulla
U
Wallin
Håkan
H
D000818:Animals; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002244:Carbon / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000032:analysis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001335:Vehicle Emissions / Q000633:toxicity*
D015850:Interleukin-6; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D002244:Carbon