Chen T H, Kavanagh T J, Chang C C, Trosko J E
Department of Pediatrics, Michigan State University, East Lansing 48824.
Cell Biol Toxicol. 1984 Oct;1(1):155-71. doi: 10.1007/BF00125572.
Gap-junctional intercellular communication is a biological process implicated in the regulation of cell proliferation and differentiation. Metabolic cooperation between 6-thioguanine-sensitive and resistant Chinese hamster cells, in vitro, has been used as a means to detect chemicals which can inhibit this form of intercellular communication. To further characterize this in vitro system as a potential screening assay for potential teratogens, tumor promoters and reproductive toxicants, a series of common solvents as well as other chemicals representing eight different functional groups, i.e., alcohols with straight or side chains, glycols, ketones, esters, ethers, phenols, aldehydes, amines and amino compounds and oxygen-heterocyclic compounds, were tested for their ability to inhibit colony-formation and to inhibit metabolic cooperation. A wide range of effects were observed which suggested a structure/activity relationship between a chemical's ability to inhibit gap junction-mediated intercellular communication and the cytotoxicity of a chemical. Possible mechanisms affecting the modulation of gap junctional communication by these chemicals are discussed.
间隙连接细胞间通讯是一种与细胞增殖和分化调节有关的生物学过程。体外6-硫代鸟嘌呤敏感和抗性中国仓鼠细胞之间的代谢合作已被用作检测可抑制这种细胞间通讯形式的化学物质的一种手段。为了进一步将这个体外系统表征为一种潜在的致畸剂、肿瘤促进剂和生殖毒物的潜在筛选试验,测试了一系列常见溶剂以及代表八个不同官能团的其他化学物质,即直链或侧链醇、二醇、酮、酯、醚、酚、醛、胺和氨基化合物以及含氧杂环化合物,检测它们抑制集落形成和抑制代谢合作的能力。观察到了广泛的效应,这表明化学物质抑制间隙连接介导的细胞间通讯的能力与其细胞毒性之间存在结构/活性关系。讨论了影响这些化学物质对间隙连接通讯调节的可能机制。