The roles of diesel exhaust particle extracts and the promotive effects of NO2 and/or SO2 exposure on rat lung tumorigenesis.
This experiment was carried out to clarify the roles of diesel exhaust particle (DEP) extracts and the promotive effects of nitrogen dioxide (NO2) and/or sulfur dioxide (SO2) exposure on rat lung tumorigenesis. F344 male rats were intratracheally administered DEP extract-coated carbon black particles (DEcCBP) and exposed to 6 ppm NO2 and/or 4 ppm SO2 for 10 months. At 18 months after starting the experiment, lung lesions were histopathologically investigated and DNA in rat lungs was analyzed for the presence of adducts using the 32P-postlabeling assay. Infiltration of alveolar macrophages, which was significant in the lungs of rats administered carbon black particles, was not prominent in those administered DEcCBP. DEcCBP occasionally formed small hyaline masses in the alveolar ducts and alveolar bronchiolization developed in the epithelium of alveolar ducts near the masses. Lung tumorigenesis and DNA aduct formation were observed in the animals administered DEcCBP with exposure to NO2 and/or SO2, but not in those administered DEcCBP alone. The results of the present study suggested that DEP extracts eluting from the small masses cause DNA damage in alveolar epithelial cells and alveolar epithelial cell proliferation, and that NO2 and/or SO2 exposure promote lung tumor induction by DEP extracts.
Department of Environmental Health, Tokyo Metropolitan Research Laboratory of Public Health, Japan. ohyama@tokyo-eiken.go.jp
K
K
Ohyama
T
T
Ito
M
M
Kanisawa
D000818:Animals; D003043:Cocarcinogenesis; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts; D004333:Drug Administration Routes; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D011916:Rats, Inbred F344; D013458:Sulfur Dioxide / Q000633:toxicity*; D014132:Trachea; D001335:Vehicle Emissions / Q000633:toxicity*
D018736:DNA Adducts; D001335:Vehicle Emissions; D013458:Sulfur Dioxide; D004247:DNA; D009585:Nitrogen Dioxide