Active oxygen transforms murine myeloid progenitor cells in vitro.
Active oxygen transforms murine myeloid progenitor cells in vitro.
复制标题
活性氧在体外转化小鼠骨髓祖细胞。
DOI：
10.1002/ijc.2910490519
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发表时间：
1991
影响因子：
6.4
通讯作者：
Greenberger,JS
中科院分区：
文献类型：
--
作者：
Crawford,DR;Greenberger,JS
活性氧（AO）在自然界中无处不在，它的多种形式可以作为天然致癌物。研究了它们对小鼠髓系祖细胞系转化的影响，以甲基纤维素中不依赖锚定的集落形成为主要实验。对过氧化氢丁基、过氧化氢和甲萘酮的细胞毒性和无毒浓度进行了检测。在非细胞毒性浓度下，即使经过多达25次的处理，也没有观察到这些细胞从白细胞介素- 3依赖性转化为因子独立性（FI）。然而，在细胞毒性浓度下，所有3类AO都将细胞转化为FI生长。效果最好的是过氧化丁基（诱导率为43倍），其次是过氧化氢，最后是美萘酮。只要一次暴露于这些氧化剂的细胞毒性水平，就会引起显著的转化，其相对效力与多次暴露所观察到的相同。这些诱导不是由于一般的细胞毒性作用，因为氟化钠和热休克治疗的诱导作用最小。甲基纤维素中AO诱导的菌落被移除，检查，然后注射到预照射的小鼠中，均匀地产生肿瘤。对照组，未处理的细胞不形成肿瘤。在较低的电镀密度下，致瘤细胞在甲基纤维素中不形成菌落。此外，与高密度培养的转化细胞相比，少量转化细胞与高密度培养的正常细胞相比，集落数量的增加幅度很小，但不足。我们的结果表明，转化体依赖于由转化细胞介导的旁分泌生长机制。对选定的因子依赖细胞系和针对白细胞介素- 3、白细胞介素- 4、粒细胞-巨噬细胞-和巨噬细胞-集落刺激因子的抗体的研究表明，这种假定的旁分泌因子是独特的。
Active oxygen (AO) is ubiquitous in nature and its many forms can act as natural carcinogens. Their effect on the transformation of a mouse myeloid progenitor cell line was studied using anchorage‐independent colony formation in methylcellulose as the primary assay. Both cytotoxic and non‐toxic concentrations of t‐butylhydroperoxide, hydrogen peroxide and menadione were examined. At non‐cytotoxic concentrations, no AO transformation of these cells from interleukin‐3 dependence to factor independence (FI) was observed, even after as many as 25 treatments. At cytotoxic concentrations, however, all 3 classes of AO transformed the cells to FI growth. The most potent agent was t‐butyl hydroperoxide (43‐fold induction), followed by hydrogen peroxide and then menadione. As little as one exposure to cytotoxic levels of these oxidants induced significant transformation, with relative potencies the same as those observed for multiple exposures. These inductions were not due to general cytotoxic effects, since sodium fluoride and heat‐shock treatment gave minimal inductions. AO‐induced colonies in methylcellulose that were removed, examined and then injected into pre‐irradiated mice uniformly produced tumors. Control, non‐treated cells did not form tumors. Tumorigenic cells did not form colonies in methylcellulose at lower plating densities. Furthermore, low numbers of transformed cells supplemented to high density with normal cells showed a small but insufficient increase in colony number as compared with high‐density cultures of transformed cells. Our results suggest that the transformants depend upon a paracrine mechanism of growth that is mediated by the transformed cells. Studies on selected factor‐dependent cell lines and antibodies to interleukin‐3, interleukin‐4, granulocyte‐macrophage‐ and macrophage‐colony stimulating factors, suggest that this putative paracrine factor is unique.