Fertilizing or contaminating?
Fertilizing or contaminating?
复制标题
施肥还是污染？
作者：
P. Olive
硝基杂环已被证明可以抑制培养的 L-929 细胞对 3H-TdR 的掺入，抑制程度与其电子亲和力有关。根据呋喃西林、米索硝唑和甲硝唑的化学反应性和潜在的临床用途，对它们抑制DNA合成的机制进行了更详细的研究。双同位素标记与羟基磷灰石色谱相结合，可以评估药物对 DNA 复制子起始、DNA 链延长和 DNA 损伤（单链断裂）的影响，以及它们与最终细胞活力的相关性。 DNA 合成起始的部分抑制通常先于其他可测量的效应，并且在没有药物的情况下孵育不会逆转。在没有 DNA 链断裂的情况下（低药物剂量或修复间隔后），经过处理和未经处理的细胞群的伸长率相似。可测量的 DNA 损伤（链断裂）可预测细胞毒性。在较低药物剂量或有氧条件下，DNA 合成并不总是与铺板效率（细胞毒性）的降低相关，而是反映在细胞集落大小（生长速率）的降低上。因此，先前报道的长期暴露于这些物质的有氧“毒性”可以更好地描述为“细胞抑制”效应。在厌氧条件下（细胞杀伤力更大），起始抑制的作用不太重要，硝基杂环化合物通过代谢还原为真正具有细胞毒性的中间体。
Nitroheterocycles have been shown to inhibit the incorporation of 3H-TdR by cultured L-929 cells, and the degree of inhibition is related to their electron-affinity. On the basis of their chemical reactivity and potential clinical utility, nitrofurazone, misonidazole and metronidazole were selected for more detailed studies of the mechanism of inhibition of DNA synthesis. Double-isotope labelling in conjunction with hydroxyapatite chromatography allowed the evaluation of drug effects on initiation of DNA replicons, DNA chain elongation and DNA damage (single-strand breaks), and their correlation with eventual cell viability. Partial inhibition of initiation of DNA synthesis generally preceded other measurable effects, and was not reversed by incubation in the absence of drug. In the absence of DNA strand breaks (at low drug doses or after a repair interval) the rate of elongation was similar in both treated and untreated cell populations. Measurable DNA damage (strand breaks) was predictive for cytotoxicity. At lower drug doses, or under aerobic conditions, DNA synthesis was not always associated with a decrease in plating efficiency (cytotoxicity) but was reflected in decreased colony size (growth rate) of the cells. Thus the aerobic "toxicity" previously reported for chronic exposure to these agents may be better described as a "cytostatic" effect. Under anaerobic conditions (where cell killing is much greater) inhibition of initiation plays a less important role, and the nitroheterocycles are metabolically reduced to intermediates which are truly cytotoxic.