Epidemiologic and experimental studies document a synergistic effect of
asbestos and smoking in the induction of
bronchogenic carcinoma. Whereas the increased risk of these
cancers in nonsmoking
asbestos workers is 4-fold or less in comparison to nonsmokers in the general population, individuals who
smoke and are exposed to
asbestos occupationally have a 80-90 fold increased risk. The observations summarized above provide substantial insight into the interactions between
asbestos and chemical
carcinogens in cigarette
smoke at the cellular level (Fig. 8). On the one hand,
asbestos fibers and other particulates appear to act as condensation nuclei for PAH in the occupational setting or environment. They then facilitate the transfer of these chemical
carcinogens into target cells, i.e., those destined to develop into
tumor cells. As a result, the adduct formation of PAH to
DNA is encouraged, an event linked intrinsically to initiation of transformation. Alternatively,
asbestos appears to enhance and modulate the further development of initiated cells to neoplastic cells by a process resembling
tumor promotion in mouse skin. In this regard, the most dramatic example illustrating the importance of
asbestos in two-stage
carcinogenesis is an experiment by Topping and Nettesheim. These investigators inserted the PAH, 7,12-dimethyl-benz(a)anthracene (DMBA) into the lumen of rat trachea which then were implanted on syngeneic animals. Subsequently,
chrysotile asbestos was introduced, and grafts were removed for histology when palpable
tumors occurred. At non-tumorigenic (i.e., initiating) amounts of DMBA,
asbestos promoted the development of
malignancies, although two
neoplasms were observed with use of
asbestos alone.
Asbestos was not carcinogenic at these amounts, but a low incidence (5%) of
squamous cell carcinoma was observed with use of
chrysotile alone at much higher concentrations. These results suggest that
asbestos is a weak
carcinogen, but more importantly a promoter of
carcinogenesis in the respiratory tract. Studies in this laboratory show striking effects of
asbestos fibers on cell proliferation and differentiation although these responses appear to occur also after exposure of tracheobronchial cells to nonasbestos fibers including fiberglass.