Detection of poly(ADP-ribose) synthetase activity in alveolar macrophages of rats exposed to nitrogen dioxide and ozone.
The toxic effects of nitrogen dioxide (NO2) and ozone (O3) are mediated through the formation of free radicals, which can cause DNA strand breaks. The present study demonstrates that exposure to NO2 and O3 causes a stimulation of poly(ADP-ribose) (polyADPR) synthetase in alveolar macrophages of rats. Three-month-old male Sprague-Dawley rats, specific pathogen free, were exposed to either 1.2 ppm NO2 or 0.3 ppm O3 alone or a combination of these 2 oxidants continuously for 3 days. The control group was exposed to filtered room air. To evaluate whether exposure to these two oxidants (NO2 and O3) caused DNA damage to lung cells, the activity of polyADPR synthetase was measured. Cellular DNA repair is dependent upon the formation of poly(ADP-ribose) polymerase, which is catalyzed by polyADPR synthetase. PolyADPR synthetase is known to be activated in response of DNA damage. The results showed that the enzyme activity was stimulated after exposure to O3 or exposure to NO2 + O3. Ozone exposure caused a 25% increase in the enzyme activity as compared to the control. Combined exposure to NO2 + O3 showed a 53% increase in the enzyme activity. These results were statistically significant as compared to the control and NO(2) exposure groups. Other parameters such as total cell count, cell viability, and differential cell count were also determined. The stimulation of polyADPR synthetase activity after O3 exposure or NO2 + O3 exposure reflects a response to lung cellular DNA repair, which may be used as an indicator for assessing DNA damage caused by oxidant injury.
Bermúdez
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Environmental Health Program, Department of Health and Safety, School of Health and Human Performance, Indiana State University, Arena B-72, Terre Haute, IN 47809, USA. hselieze@scifac.indstate.edu
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004338:Drug Combinations; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
D004338:Drug Combinations; D011064:Poly Adenosine Diphosphate Ribose; D010126:Ozone; D009585:Nitrogen Dioxide