QUANTITATIVE STUDIES ON CONCURRENT FACTORS IN NEOPLASTIC TRANSFORMATION

小鼠胚胎转化机制的研究 继续培养BALB/3T3克隆A-31-1-1细胞。(1) 用几种金属实现了相变。这个 三价和三价联苯的毒性和转化机制 对五价砷(As)进行了研究。原样三价 发现其活性是五价砷的4倍。蜂窝 通过代谢减少，三价形式的摄取率更高 过程部分依赖于谷胱甘肽。当与关联时 计算为细胞负荷、毒性和转化率 发现两种形式的AS的频率是相同的。单元格 暴露在五价元素中，释放出三价形式进入 5~6成熟。没有发现甲基化的代谢物，表明缺乏 在这个细胞系中的这种解毒机制。结果是 表明三价As是导致有毒物质的形式 和转化效应，与价态无关 砷暴露。 (2)哇巴因诱导动力学的研究： N-乙基-N-亚硝脲诱发的耐药突变 重复BALB/3T3细胞，并使用较大的 单元格数量。 (3)接种裸鼠后，BALB/3T3细胞发生转化。 通过砷，通过其他致癌物，或自发地发现 致癌但不转移，与缺乏 在这些细胞系中观察到IV型胶原溶解活性。 通过进一步治疗来诱导转移活性 RAS癌基因或与致癌物的关系正在调查中。

Studies on mechanisms of transformation in the mouse embryo BALB/3T3 clone A-31-1-1 cell line were continued. (1) Transformation was obtained with several metals. The mechanisms of toxicity and transformation by both trivalent and pentavalent arsenic (As) were investigated. Trivalent As was found to be 4 times more active than pentavalent As. Cellular uptake was higher for trivalent form by a metabolic reduction process partly dependent on glutathione. When correlated with the calculated As cell burden, toxicity and transformation frequency were found to be the same for both forms of As. Cells exposed to pentavalent As released the trivalent form into the medium. No methylated metabolites were found, indicating lack of this detoxification mechanism in this cell line. The results indicate that trivalent As is the form responsible for the toxic and transforming effects, independent of the valence state of the As exposure. (2) Previous studies on the induction kinetics of ouabain- resistant mutations induced by N-ethyl-N-nitrosourea in BALB/3T3 cells were repeated and fully confirmed using larger numbers of cells. (3) When inoculated in nude mice, BALB/3T3 cells transformed by As, by other carcinogens, or spontaneously, were found to be tumorigenic but not metastasizing, in keeping with the lack of type IV collagenolytic activity observed in these cell lines. Induction of metastatic activity by further treatment with the ras oncogene or with carcinogens in under investigation.