NYC-WTC_000195068

NYC 9/11 Public Portal Document

ASBESTOS MEDITEXT (s) - Medical Mariagenient Page 2 of 3

have not been completely elucidated. Two currently popular theories (not mutually exclusive) involve a central role of oxygen radicals generated by the asbestos fibers, versus induction of various growth factors and cytokines to mediate fibrosis (Brody, 1993). 1. With asbestos inhalation, alveolar macrophages accumulate at the area of fiber deposition (Mossman et al, 1990). 2. With phagocytosis of the fiber, the activated macrophages produce a mixture of fibroblast growth factors, chemoattractants, fibronectin, prostaglandins, procoagulants, leukotriene B4, lysozomal enzymes, active oxygen metabolites, tumor necrosis factor­ alpha, and interleukin 1 (ATSDR, 1990; Bissonnette et al, 1990; Callahan et al, 1990; Dark & Pingleton, 1983; Elferink et al, 1989; Garcia et al, 1989; Goodglick et al, 1989; Goodglick & Kane, 1990; Hayes et al, 1988; HSDB, 1995; Iguchi & Kojo, 1989; Kagan, 1988; Mossman et al, 1990; Roney & Holian, 1989; Schwartz et al, 1989; Ljungman et al, 1994). 3. Lung injury can be induced by an asbestos-related increase in neutrophils which release a collagenase and neutrophil chemotactic factors (Delclos et al, 1989; Garcia et al, 1989; Hayes et al, 1988; Mossman & Gee, 1989). 4. These inflammatory mediators incite widespread tissue destruction, granuloma formation, and pulmonary fibrosis (ATSDR, 1990; Callahan et al, 1990; Chang et al, 1988; Dark & Pingleton, 1983; Garcia et al, 1989; Hayes et al, 1988; Kagan, 1988; Schwartz et al, 1989). 5. Once inside the macrophages, the fibers may be coated with a mucopolysaccharide and iron matrix, thus forming the drumstick configuration of the ferruginous asbestos bodies (ATSDR, 1990; Dark & Pingleton, 1983). In asbestosis, coated fibers may be much fewer than uncoated fibers which exert the most damage (Dark & Pingleton, 1983). 6. Because the fibers concentrate in the lower lung fields, fibrosis tends to occur first in the lung bases; pleural effects are generally confined to the lower two-thirds of the thorax. 7. Plaques are formed when sharp fibers (such as anthrophyllite) penetrate into the pleura during breathing or via the lymphatic system (Dark & Pingleton, 1983). 8. Asbestos fibers can also penetrate to the terminal bronchioles and elicit a fibrogenic response upon entry into the peribronchiolar space (ATSDR, 1990). 9. The pneumoconiotic reaction appears to be more closely related to the surface area as opposed to the number of retained fibers per gram of lung tissue (Becklace, 1991). C. CARCINOGENESIS - The mechanism(s) by which asbestos can induce cancer is not known. It is unclear whether or not asbestos can induce carcinogenesis by initiating a heritable genetic change and promoting this with proliferative and genotypic changes (Mossman et al, 1990). 1. The reactive oxygen metabolites produced in asbestos-induced lipid peroxidation can cause mutations, DNA strand breaks, chromosomal breaks, nuclear changes, and epigenetic changes (Goodglick & Kane, 1990). 2. Because 144 patients with asbestos-related mesotheliomas had important differences from the epidemiological pattern of asbestos-related bronchogenic cancer, it was suggested that asbestos may not act as a complete carcinogen, but rather as a promoter (Browne, 1983). 3. Longitudinal and cross-sectional data from a brake manufacturing plant also suggest the irritant role of asbestos (Pames, 1990). 4. Asbestos absorbs carcinogens like benzo(a)pyrene and catalyzes the oxidation of weak to potent carcinogens (Dunn, 1989). Hydrogen peroxide in cigarette smoke and asbestos may induce DNA strand breaks via a hydroxyl radical dependent mechanism. 5. The development of mesothelioma seems to be related to the length and diameter of fibers and to prolonged exposure, although there have been reports with very minimal asbestos exposure (Dunn, 1989). Unlike bronchogenic carcinoma, there is no association

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