石棉致癌作用的细胞和分子机制：对生物持久性的影响。
Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence.
作者信息
Barrett J C
机构信息
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
出版信息
Environ Health Perspect. 1994 Oct;102 Suppl 5(Suppl 5):19-23. doi: 10.1289/ehp.94102s519.
Carcinogenic agents can influence the carcinogenic process either by mutating critical target genes or by increasing the number of cells at risk for mutations. Cytogenetic and molecular studies of asbestos-related cancers indicate that inactivation or loss of multiple tumor suppressor genes occurs during lung cancer development. Aneuploidy and other chromosomal changes induced by asbestos fibers may be involved in genetic alterations in asbestos-related cancers. Furthermore, asbestos fibers may influence the carcinogenic process by inducing cell proliferation, free radicals, or other promotional mechanisms. Therefore, asbestos fibers may act at multiple stages of the carcinogenic process by both genetic and epigenetic mechanisms. Biopersistence is undoubtedly important in fiber carcinogenicity. However, the time required for a fiber to remain in the lung to exert a cancer-related effect is difficult to specify.
致癌物质可通过使关键靶基因突变或增加有突变风险的细胞数量来影响致癌过程。对石棉相关癌症的细胞遗传学和分子研究表明，在肺癌发展过程中会发生多个肿瘤抑制基因的失活或缺失。石棉纤维诱导的非整倍体和其他染色体变化可能与石棉相关癌症的基因改变有关。此外，石棉纤维可能通过诱导细胞增殖、自由基或其他促进机制来影响致癌过程。因此，石棉纤维可能通过遗传和表观遗传机制在致癌过程的多个阶段起作用。生物持久性无疑在纤维致癌性中很重要。然而，纤维在肺部停留以产生与癌症相关影响所需的时间很难确定。
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