RESPIRATORY CARCINOGENESIS BY CHEMICAL AND PHYSICAL FACTORS

1998年1月31日退休后，萨菲奥蒂博士继续担任荣休科学家，并与其他研究人员合作。他的主要研究重点是呼吸道致癌机制，特别是那些导致结晶二氧化硅颗粒对周围肺上皮细胞致癌活性的机制，以及二氧化硅颗粒的细胞毒性、纤维化和上皮致癌之间的关系。一项关于结晶二氧化硅多晶型方石英的物理化学表面性质在确定其生物活性中的作用的研究已经完成并发表。用大鼠肺泡细胞系AE6、小鼠单核巨噬细胞瘤细胞系J774和大鼠肺泡巨噬细胞对方石英粉尘样品进行逐级升温至1300oC后的差示活性测定。在所有情况下，加热到800oC会显著降低方石英的活性，而加热到1300oC则会消除这种活性。电子顺磁共振显示，表面自由基在加热过程中逐渐退火，在800oC或更高温度下大部分消失；水蒸气吸附表明，在800oC加热后，表面仍有亲水路径，但在1300oC加热后，表面完全疏水。虽然1300oC的加热对粉尘的粒度分布和形貌没有明显的影响，但通过氮气吸附测量，粉尘比表面积减小，表明已经发生了微裂纹的烧结。结果证实了二氧化硅表面羟基在决定二氧化硅生物活性中的关键作用。它们在诱导肿瘤转化中的作用还需要进一步研究。用抗转化生长因子β受体、肾上腺髓质素受体和肾上腺髓质素蛋白的抗体，用免疫组织化学方法研究了结晶性二氧化硅颗粒对大鼠肺细胞分子标志物的诱导作用。初步结果显示，染矽尘的大鼠肺内的内分泌细胞数量逐渐增加。-人体组织、体液、细胞等。

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.