Mechanisms of the combined effect of asbestos and smoking in the etiology of lung cancer.

The joint effects of exposure to two known lung carcinogens, tobacco smoking and asbestos, are reviewed. The variable pattern of interaction--ranging from supramultiplicative to less than additive--may reflect the fact that both asbestos and smoking are complex carcinogens which can affect more than one stage of lung carcinogenesis. The joint effect of two such agents will depend on the relative magnitude of the effects at each stage. The epidemiologic evidence from studies of insulation workers with high exposures suggests an interaction that approximates the multiplicative model, indicating that each of the two factors has an independent action on the multistage process of carcinogenesis. Very limited information is available on the interaction between these two agents in causing specific histological types of lung cancer. Both tobacco smoke and asbestos fibers can be genotoxic and cytotoxic and cause proliferative lesions in the lungs. Tobacco smoke is known to contain carcinogens that bind to critical genes in DNA (deoxyribonucleic acid) and cause mutations. Asbestos fibers may cause chronic inflammation of the lungs, which releases various cytokines and growth factors, and therefore may provide a possible selective growth advantage for mutated cells.