Oxidative stress to DNA, protein, and antioxidant enzymes (superoxide dismutase and catalase) in rats treated with benzo(a)pyrene.
Oxidative DNA damage (as 8-hydroxydeoxyguanosine; 8-OHdG), carbonyl content of proteins, and activities of superoxide dismutase (SOD) and catalase were investigated in female Sprague-Dawley rats orally treated with benzo(a)pyrene (B(a)P) (75 mg/rat). HPLC-ECD system showed that B(a)P increased the level of 8-OHdG in tissues (liver, kidney, and lung), but a statistical significance was observed only in the liver (3.5-fold increase) and kidney (two-fold increase). In the liver, the peak level (21 +/- 5 8-OHdG residues/10(5) dG) was obtained 12 h after treatment and returned close to control level (9 +/- 2 8-OHdG residues/10(5) dG) at 24 h, but 8-OHdG was persistent in the kidney. Carbonyl contents measured as an index of protein oxidation were slightly increased (23-35%) in the cytosolic fraction of tissues, but a significant increase (2.19 nmol/mg protein, 35% increase) was observed only in the liver 6 h after treatment, similar to 8-OHdG. However, the rate of increase was relatively low compared to that of 8-OHdG. In contrast to DNA and protein damages, the activities of SOD and catalase in the tissues were decreased after treatment (P < 0.01) and gradually increased to control levels. SOD and catalase activities in organs of rats were inversely correlated with oxidative damages to DNA and protein. The data suggest that B(a)P oxidatively altered DNA, protein, and antioxidant enzymes in rats and this might be associated with B(a)P carcinogenesis.
Kim
K B
KB
Division of Toxicology, School of Pharmacy, Sung Kyun Kwan University, Suwon, Kyunggi-Do, South Korea.
Lee
B M
BM
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors
D002273:Carcinogens; D011506:Proteins; D001564:Benzo(a)pyrene; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D002374:Catalase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine