Cocarcinogenic and tumor promoting properties of asbestos and other minerals in tracheobronchial epithelium.
Cocarcinogenic and tumor promoting properties of asbestos and other minerals in tracheobronchial epithelium.
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气管支气管上皮中石棉和其他矿物质的致癌和促肿瘤特性。
DOI：
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发表时间：
1985
期刊：
影响因子：
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通讯作者：
L. Yotti
中科院分区：
文献类型：
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作者：
B. Mossman;G. Cameron;L. Yotti
流行病学和实验研究证明石棉和吸烟在诱发支气管肺癌方面具有协同作用。与一般人群中的非吸烟者相比，非吸烟石棉工人患这些癌症的风险增加了4倍或更少，而吸烟并在职业上暴露于石棉的个人的风险增加了80-90倍。以上总结的观察结果为石棉与香烟烟雾中化学致癌物在细胞水平上的相互作用提供了实质性的见解（图8）。一方面，石棉纤维和其他颗粒物似乎在职业设置或环境中充当PAH的凝结核。然后，它们促进这些化学致癌物转移到靶细胞中，即，那些注定要发展成肿瘤细胞的细胞。因此，PAH与DNA的加合物形成受到鼓励，这是一个与转化起始内在相关的事件。另外，石棉似乎通过类似于小鼠皮肤中肿瘤促进的过程来增强和调节起始细胞向肿瘤细胞的进一步发展。在这方面，说明石棉在两阶段致癌作用中的重要性的最引人注目的例子是Topping和Nettesheim的实验。这些研究人员将PAH，7，12-二甲基-苯并（a）蒽（DMBA）插入大鼠气管腔内，然后将其植入同基因动物。随后，温石棉被引入，当出现明显的肿瘤时，移植物被移除进行组织学检查。在非致瘤性（即，初始）量的DMBA，石棉促进恶性肿瘤的发展，尽管单独使用石棉观察到两种肿瘤。石棉在这些含量下不具有致癌性，但在单独使用浓度高得多的温石棉时，观察到鳞状细胞癌的发生率较低（5%）。这些结果表明，石棉是一种弱致癌物，但更重要的是在呼吸道致癌的促进剂。本实验室的研究表明，石棉纤维对细胞增殖和分化有显著影响，尽管这些反应似乎也发生在气管支气管细胞暴露于非石棉纤维（包括玻璃纤维）后。
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.