Modification of the proteinase/anti-proteinase balance in the respiratory tract of Sprague-Dawley rats after single intratracheal instillation of benzo[a]pyrene-coated onto Fe2O3 particles

Available data suggest that repeated concurrent exposure to haematite (Fe2O 3) and benzo[a]pyrene (B[a]P) results in a decreased latency and an increas ed incidence of lung tumours in rodents compared to exposure to B[a]P alone . Moreover, the reactive oxygen species (ROS) formed by the lung cells them selves and/or by activated inflammatory cells may possibly contribute to th e development of pulmonary disorders such as cancer formation. In order to investigate the precise role of iron in the injury induced by B[a]P-coated onto Fe2O3 particles, we tend to address the hypothesis that Fe2O3 and B[a] P, alone or in association, can induce oxidative stress conditions (malondi aldehyde) and/or inflammatory reactions (interleukin-6) and thereby disrupt the proteinase/anti-proteinase balance (cathepsins B and L, polynuclear ne utrophil (PNN) elastase, alpha-1 proteinase inhibitor (alpha(1)PI) and its inhibitory capacity) in the rat respiratory tract. Thus, Fe2O3 or B[a]P-coa ted onto Fe2O3 particles produce oxidative stress conditions through not on ly iron-catalysed oxidative reactions but also inflammatory processes. Howe ver, B[a]P initiates only inflammatory responses. These pollutants generate increased levels of proteases and decrease the concentrations of free alph a(3)PI, There is also a clear relationship between the partial inactivation of alpha(1)PI and the occurrence of ROS after exposure to Fe2O3, alone or as a carrier of B[a]P, Hence, the proteinase/anti-proteinase balance might be more disrupted by Fe2O3 or B[a]P-coated onto Fe2O3 particles than by B[a ]P alone. These results suggest a mechanism that can explain why B[a]P-coat ed onto Fe2O3 particles are more injurious than B[a]P alone. Copyright (C) 2000 John Wiley & Sons, Ltd.