Inhalation of ozone induces DNA strand breaks and inflammation in mice.
Ozone (O3) is a well-known oxidant pollutant present in photochemical smog. Although ozone is suspected to be a respiratory carcinogen it is not regulated as a carcinogen in most countries. The genotoxic and inflammatory effects of ozone were investigated in female mice exposed to ozone for 90 min. The tail moment in bronchoalveolar lavage (BAL) cells from BALB/c mice was determined by the comet assay as a measure of DNA strand breaks. Within the first 200 min after exposure, the BAL cells from the mice exposed to 1 or 2 ppm ozone had 1.6- and 2.6-fold greater tail moments than unexposed mice. After 200 min there was no effect. It could be ruled out that the effect during the first 200 min was due to major infiltration of lymphocytes or neutrophils. Unexpectedly, ozone had no effect on the content of 8-oxo-deoxyguanosine (8-oxo-dG) in nuclear DNA or on oxidised amino acids in the lung tissue. The mRNA level of the repair enzyme ERCC1 was not increased in the lung tissue. Inflammation was measured by the cytokine mRNA level in lung homogenates. An up to 150-fold induction of interleukin-6 (IL-6) mRNA was detected in the animals exposed to 2 ppm ozone compared to the air-exposed control mice. Also at 1 ppm ozone, the IL-6 mRNA was induced. The large induction of IL-6 mRNA in the lung took place after DNA strand breaks were induced in BAL. This does not support the notion that inflammatory reactions are the cause of DNA damage. To determine whether these exposures were mutagenic, Muta Mice were exposed to 2 ppm ozone, 90 min per day for 5 days. No treatment-related mutations could be detected in the cII transgene. These results indicate that a short episode of ozone exposure at five times the threshold limit value (TLV) in US induces lung inflammatory mediators and DNA damage in the cells in the lumen of the lung. This was not reflected by an induction of mutations in the lung of Muta Mice.
Bornholdt
Jette
J
National Institute of Occupational Health, Lersø Park Allé 105, DK-2100, Copenhagen, Denmark.
Dybdahl
Marianne
M
Vogel
Ulla
U
Hansen
Max
M
Loft
Steffen
S
Wallin
Håkan
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D001980:Bronchi / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004268:DNA-Binding Proteins; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004720:Endonucleases; D005260:Female; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D010455:Peptides; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; C110490:mutacin II prepeptide, bacteria; D010126:Ozone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004720:Endonucleases; C499360:Ercc1 protein, mouse; D003849:Deoxyguanosine