RESPIRATORY CARCINOGENESIS BY CHEMICAL AND PHYSICAL FACTORS

1998年1月31日退休后，Saffiotti博士继续以荣誉科学家的身份工作，并与其他研究人员合作。主要研究方向为呼吸道癌变机制，特别是肺外周上皮结晶二氧化硅颗粒的致癌性机制，以及二氧化硅颗粒的细胞毒性、纤维形成与上皮癌变之间的关系。一项研究已经完成并发表的作用的物理-化学表面性质的结晶硅多晶，方石英，在决定其生物活性。采用大鼠肺泡细胞系AE6、小鼠单核-巨噬细胞肿瘤细胞系J774和大鼠肺泡巨噬细胞，在逐渐加热至1300℃后，测量了方石石粉尘样品的差异活性。在所有情况下，加热到800℃大大降低了方石英的活性，加热到1300℃则消除了方石英的活性。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以上基本消失；水蒸气吸附表明，在800℃加热后表面仍有亲水通道，而在1300℃加热后表面完全疏水。虽然在1300℃下加热对颗粒的尺寸分布和形貌没有太大影响，但通过氮吸附测量粉尘表面积减小，表明微裂纹已经发生烧结。结果证实了二氧化硅表面羟基在决定二氧化硅生物活性方面的关键作用。它们在诱导肿瘤转化中的作用有待进一步研究。采用免疫组织化学方法，利用TGF β受体、肾上腺髓质素受体和PAMP（肾上腺髓质素蛋白）抗体，研究大鼠肺细胞与结晶二氧化硅颗粒反应过程中分子标志物的诱导作用。初步结果表明，二氧化硅处理的大鼠肺部内分泌细胞数量呈进行性增加。-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.