DNA synthesis in pulmonary alveolar macrophages and type II cells: effects of ozone exposure and treatment with alpha-difluoromethylornithine
An increase in the number of pulmonary alveolar macrophages (AM) can be induced by a number of toxic insults to the lung, including ozone, an important photochemical oxidant air pollutant. This increase could arise from an influx of monocytes from the vascular or interstitial compartments, or from proliferation of AM in situ. While proliferation of alveolar type II cells after oxidant exposure has been well documented, it is not clear whether AM are also capable of this response. Rats were exposed to air or to 0.12, 0.25, or 0.50 ppm ozone for 1, 2, 3, 7, or 14 d, 20 h/d. The labeling index in both AM and type II cells increased about 10-fold after 2 d of exposure to 0.25 and 0.50 ppm of ozone, but returned to control levels by the end of 1 wk of exposure. These changes closely paralleled the temporal and dose-response characteristics of changes in total lung DNA synthesis. alpha-Difluoromethylornithine (DFMO) administered to rats during a 2-d exposure to 0.50 ppm ozone did not inhibit the ozone-induced increase in labeling index in AM or type II cells, although evidence of inhibition of lung ornithine decarboxylase activity was obtained, and the ozone-induced increase in total lung DNA synthesis was inhibited by 23%. These results suggest that, like type II cells, AM are capable of entering the cell cycle and synthesizing new DNA in situ in response to short-term exposure to environmentally relevant doses of ozone, and that the ozone-induced stimulation of DNA synthesis in these cell types was refractory to inhibition by DFMO.
- Research Organization:
- General Motors Research Laboratories, Warren, MI
- OSTI ID:
- 6403505
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Vol. 1-2
- Country of Publication:
- United States
- Language:
- English
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DECARBOXYLASES
ENZYME ACTIVITY
MACROPHAGES
DNA REPLICATION
OZONE
TOXICITY
AIR POLLUTION
CELL CYCLE
CELL PROLIFERATION
DOSE-RESPONSE RELATIONSHIPS
LUNGS
MITOTIC INDEX
RATS
THYMIDINE
ANIMAL CELLS
ANIMALS
AZINES
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CONNECTIVE TISSUE CELLS
ENZYMES
HETEROCYCLIC COMPOUNDS
LYASES
MAMMALS
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHAGOCYTES
POLLUTION
PYRIMIDINES
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology