ASBESTOS-INDUCED LUNG-DISEASE

This review attempts to deal with two major questions concerning asbes tos-induced lung disease: How does inhaled asbestos cause cell prolife ration and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the p ast 10 years, and there appear to be two hypothetical schemes which co uld explain, at least in part, the fibroproliferative effects of asbes tos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first , but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple var ieties of growth factors and cytokines that mediate the pathogenesis o f asbestosis. There is increasing evidence that molecules such as plat elet-derived growth factor and transforming growth factor beta, both s ynthesized and secreted by activated lung macrophages, are responsible , respectively, for the increased interstitial cell populations and ex tracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis. The challenge today is to establish which combinations of t he many factors released actually are playing a role in disease pathog enesis. The issue of continued risk currently is more a question of po licy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances und er which asbestos in buildings constitutes an ongoing health hazard. T he litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a c omplete carcinogen. It appears to be generally nongenotoxic, but all a sbestos fiber tv pes can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation .