Mechanisms of asbestos-induced carcinogenesis.

Respiratory exposure to asbestos fibers has been associated with diffuse malignant mesothelioma (DMM) in humans. Despite advancements in the molecular analyses of human DMM and the development of animal models, the carcinogenic mechanisms of the disease remain unclear. There are basically three hypotheses regarding the pathogenesis of asbestos-induced DMM, which may be summarized as follows: (1) the "oxidative stress theory" is based on the fact that phagocytic cells that engulf asbestos fibers produce large amounts of free radicals due to their inability to digest the fibers, and epidemiological studies indicating that iron-containing asbestos fibers appear more carcinogenic; (2) the "chromosome tangling theory" postulates that asbestos fibers damage chromosomes when cells divide; and (3) the "theory of adsorption of many specific proteins as well as carcinogenic molecules" states that asbestos fibers in vivo concentrate proteins or chemicals including the components of cigarette smoke. Elucidation of the major mechanisms underlying DMM would be helpful for the development of novel strategies to prevent DMM induction in people who have already been exposed to asbestos.