Benzo(a)pyrene-coated onto Fe2O3 particles-induced lung tissue injury: role of free radicals

Lipid peroxidation (as malondialdehyde; MDA), activities of some antioxidan t enzymes (as superoxide dismutase; SOD, glutathione peroxidase; GPx, gluta thione reductase; GR), glutathione status, and oxidative DNA damage (as 8-h ydroxy-2'-deoxyguanosine; 8-OHdG) were investigated in the lungs of rats ex posed to hematite (Fe2O3; 3 mg), benzo(a)pyrene (B(a)P; 3 mg), or B(a)P (3 mg)-coated onto Fe2O3 particles (3 mg). Approximately 2-fold increases in M DA production were seen in animals exposed to Fe2O3, B(a)P, or B (a)P-coate d onto Fe2O3 particles (P < 0.01). Decreases in SOD activities were observe d in rats treated with Fe2O3, (1.66-fold, P < 0.01), B(a)P (1.66-fold, P < 0.001) or B(a)P-coated onto Fe2O3 particles (1.43-fold, P < 0.01). GPx and GR activities could not be detected. No alteration of the glutathione statu s was observed. Significant increases in the 8-OHdG formation occurred in r esponse to exposure to B(a)P (2.0-fold, P < 0.01) or B(a)P-coated onto Fe2O 3 particles (23.7-fold, P < 0.001). Our results demonstrate also that Fe2O3 generates free radical (FR)-induced lung injury and is not an inert carrie r. We established that exposure to B(a)P or B(a)P-coated onto Fe2O3 particl es resulted in lipid peroxidation and SOD inactivation, thereby leading to oxidative damages in DNA. The main findings of this work was that B(a)P-coa ted onto Fe2O3 particles caused higher lung concentrations of 8-OHdG than B (a)P by itself. Hence, our data may explain why exposure to B(a)P-coated on to Fe2O3 particles resulted in a decreased latency and an increased inciden ce of lung tumors in rodents compared to exposure to B(a)P. (C) 2001 Elsevi er Science Ireland Ltd. All rights reserved.