Stimulation of poly(ADP-ribose) synthetase activity in the lungs of mice exposed to a low level of ozone.
Toxic effects of O3 are mediated through the formation of free radicals, which can cause DNA strand breaks. Cellular DNA repair is dependent upon the formation of poly(ADP-ribose) (polyADPR) catalyzed by polyADPR synthetase. In order to evaluate whether O3 exposure inflicted DNA damage in lung tissue, we measured the activity of polyADPR synthetase (known to be activated in response to DNA damage) in mouse lungs after exposure to 0.45 ppm (882 micrograms/m3) O3 for up to 7 days. The enzyme activity was stimulated with O3 exposure relative to unexposed controls, showing a 20% (P less than 0.05) increase at Day 5 and 42% (P less than 0.001) at Day 7 of O3 exposure. In addition, the activity of superoxide dismutase (SOD), known to be stimulated in response to production of superoxide anion (.O2-), was measured as an indicator of free radical involvement. Relative to unexposed controls, the SOD activity in exposed animal lungs increased to the peak level at Day 5 (48%, P less than 0.001) and then declined at Day 7 of O3 exposure but was still higher than controls (17%, P less than 0.05). When animals, after 5 days of O3 exposure, were allowed to recover in filtered room air, the activities of both enzymes declined to their respective control values in 6 days. These results suggest a possible temporal relationship between O3 injury and the activities of polyADPR synthetase and a free radical scavenging enzyme, SOD. The stimulation of polyADPR synthetase activity with O3 exposure, reflecting a response to lung cellular DNA repair, may be a sensitive indicator for assessing DNA damage in oxidant injury.
D000818:Animals; D004260:DNA Repair; D006026:Glycoside Hydrolases / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009243:NAD / Q000032:analysis; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D010126:Ozone / Q000633:toxicity*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D009243:NAD; D010126:Ozone; D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase; D009244:NAD+ Nucleosidase