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 Fe(2)O(3) particles.

Available data suggest that repeated concurrent exposure to haematite (Fe(2)O(3)) and benzo[A]pyrene (B[A]P) results in a decreased latency and an increased 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 themselves and/or by activated inflammatory cells may possibly contribute to the 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 Fe(2)O(3) particles, we tend to address the hypothesis that Fe(2)O(3) and B[A]P, alone or in association, can induce oxidative stress conditions (malondialdehyde) and/or inflammatory reactions (interleukin-6) and thereby disrupt the proteinase/anti-proteinase balance (cathepsins B and L, polynuclear neutrophil (PNN) elastase, alpha-1 proteinase inhibitor (alpha(1)PI) and its inhibitory capacity) in the rat respiratory tract. Thus, Fe(2)O(3) or B[A]P-coated onto Fe(2)O(3) particles produce oxidative stress conditions through not only iron-catalysed oxidative reactions but also inflammatory processes. However, B[A]P initiates only inflammatory responses. These pollutants generate increased levels of proteases and decrease the concentrations of free alpha(1)PI. There is also a clear relationship between the partial inactivation of alpha(1)PI and the occurrence of ROS after exposure to Fe(2)O(3), alone or as a carrier of B[A]P. Hence, the proteinase/anti-proteinase balance might be more disrupted by Fe(2)O(3) or B[A]P-coated onto Fe(2)O(3) particles than by B[A]P alone. These results suggest a mechanism that can explain why B[A]P-coated onto Fe(2)O(3) particles are more injurious than B[A]P alone. Copyright 2000 John Wiley & Sons, Ltd.