Effects of Cigarette Smoke on Uptake of Asbestos Fibres by Tracheal Organ Cultures: The Role of Active Oxygen Species

Abstract

In order to investigate how cigarette smoke enhances asbestos fibre retention and tissue penetration, we employed a tracheal organ culture system in which the tracheal segments were initially exposed to smoke or air, subsequently exposed to a suspension of amosite asbestos, and then maintained in organ culture for varying time periods. Exposure to smoke consistently increased both the uptake of asbestos fibres by the tracheal epithelial cells and the proliferative response to asbestos by tracheal epithelial cells compared to exposure to air. This effect was seen when asbestos was added to the tracheas immediately after smoke exposure, or when asbestos exposure was delayed for up to 48 hours. Smoke enhanced uptake could be totally abolished by inclusion of superoxide dismutase or catalase with the asbestos or pretreatment of the asbestos with deferoxamine. These scavengers of active oxygen species also decreased uptake of fibres by tracheal epithelium in the absence of smoke, although, in contrast to the effects seen with smoke, protection was never complete. We conclude that: (1) Smoke enhancement of asbestos fibre uptake is a direct effect of cigarette smoke on the epithelium and does not require the participation of inflammatory cells; (2) Brief exposure to smoke primes the cell for uptake even when there is a considerable delay in asbestos exposure; (3) Active oxygen species play a role in fibre uptake and the proximate species is probably OH. derived from H202. We speculate that H2O2 is generated for long periods from smoke tar deposited on the epithelial surface.