RESPIRATORY CARCINOGENESIS BY CHEMICAL AND PHYSICAL FACTORS

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After his retirement on 1/31/98, Dr. Saffiotti has continued his work as Scientist Emeritus and collaborated with other investigators. His main focus of research is on the mechanisms of respiratory carcinogenesis, especially those responsible for the carcinogenic activity of crystalline silica particles on the peripheral lung epithelia and on the relationships between cytotoxicity, fibrogenesis and epithelial carcinogenesis of silica particles.A study has been completed and published on the role of physico-chemical surface properties of the crystalline silica polymorph, cristobalite, in determining its biological activity. Differential activity was measured on a sample of cristobalite dust, after heating at progressive temperatures up to 1300oC, using the rat lung alveolar cell line AE6, the mouse monocyte-macrophage tumor cell line J774, and rat lung alveolar macrophages. In all cases, heating to 800oC considerably reduced the activity of cristobalite and heating to 1300oC eliminated the actvity. Electron paramagnetic resonance showed that surface radicals were progressively annealed by heating, mostly disappearing at 800oC or above; water vapor adsorption showed that hydrophilic pathches remained after heating at 800oC but the surface was completely hydrophobic after heating at 1300oC. Although particle size distribution and morphology were not substantially affected by heating at 1300oC, dust surface area was decreased when measured by nitrogen adsorption, suggesting that a sintering of microcracks had occurred. The results confirmed the critical role of hydroxyl groups on the silica surface in determining the biological activity of silica. Their role in the induction of neoplastic transformation needs to be further sudied. Immunohistochemical methods were used to investigate the induction of molecular markers in the cells of the lung during their reaction to crystalline silica particles in rats, using antibodies against TGF beta receptors, adrenomedullin receptors and PAMP (adrenomedullin protein). Preliminary results indicate a progressive increase in the number of endocrine cells in the lungs of silica- treated rats. - Human Tissues, Fluids, Cells, etc.