Tumor promotion: models and assay systems.
Tumor promotion: models and assay systems.
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DOI：
10.1002/tcm.1770100205
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
D. JamesFitzgerald;H. Yamasaki
中科院分区：
文献类型：
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作者：
D. JamesFitzgerald;H. Yamasaki
肿瘤促进是由实验性致癌的两阶段模型在手术上定义的。因此，在严格意义上，仅从这样的模型中识别肿瘤促进剂是可能的。体外两阶段细胞转化试验的发展和使用是对肿瘤促进剂的体外短期测试的合乎逻辑的扩展。另一种方法是将肿瘤促进过程的机械知识应用于开发此类分析的终点。在此背景下，我们一直在使用体外和体内系统研究被阻断的缝隙连接细胞间通讯(GJIC)在肿瘤促进中的作用。许多启动子已被证明在体外阻断GJIC；我们的研究支持抑制GJIC在促进BALB/c 3T3细胞转化阶段发挥重要作用的观点。在动物实验中，我们已经证明大鼠肝脏肿瘤促进剂苯巴比妥可以降低全身暴露大鼠肝脏中32kD缝隙连接蛋白基因的表达水平。确实有必要进一步研究GJIC在肿瘤促进中的作用。此外，体外GJIC和转化检测系统的部署将为检测环境化学品的促癌活性提供有用的短期测试。
Tumor promotion is defined operationally from two-stage models of experimental carcinogenesis. It is, therefore, in a strict sense, possible to identify tumor promoters only from such models. The development and use of in vitro two-stage cell transformation assays was a logical extension toward in vitro short-term testing for tumor promoters. Another approach is to apply mechanistic knowledge of the tumor promotion process in developing end points for such assays. In this context, we have been examining the role of blocked gap-junctional intercellular communication (GJIC) in tumor promotion, using in vitro and in vivo systems. Many promoters have been shown to block GJIC in vitro; our studies support the idea that inhibition of GJIC does play an important role in the promotion stage of BALB/c 3T3 cell transformation. In animal studies, we have shown that the rat liver tumor promoter phenobarbital can decrease the level of expression of the 32 Kd gap junction protein gene specifically in liver upon systemic exposure in rats. Further examination of the role of GJIC in tumor promotion is indeed warranted. Also, deployment of in vitro GJIC and transformation assay systems should provide useful short-term tests for detecting tumor promoting activity of environmental chemicals.