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首页> 外文期刊>British Journal of Cancer >Phase-specific cytotoxicity in vivo of hydroxyurea on murine fibrosarcoma pulmonary nodules
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Phase-specific cytotoxicity in vivo of hydroxyurea on murine fibrosarcoma pulmonary nodules

机译：羟基脲对小鼠纤维肉瘤肺结节的体内阶段特异性细胞毒性

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The cytotoxic effects in vivo of hydroxyurea (HU) on murine fibrosarcoma (FSa) cells grown as pulmonary tumours were determined. Tumour cells from 13-day-old nodules were made into suspension and separated on the basis of cell size by centrifugal elutriation. Flow microfluorometry (FMF) was used to determine the cell-cycle parameters and the relative synchrony of the separated populations, as well as the degree of contamination by normal diploid cells in each of the tumour-cell populations. HU cytotoxicity was tested by administering both a single 1 mg/g i.p. dose into mice that had been injected i.v. 20 min earlier with known numbers of synchronized viable FSa cells, and i.p. doses of 1 mg/g each into mice bearing 13-day-old pulmonary nodules. In the latter experiments, animals were killed 1 h after the last dose, and the tumour nodules were excised and made into a single-cell suspension and elutriated. Known numbers of cells from each fraction were injected into recipient mice to determine survival. In both sets of experiments, cell killing by HU correlated with the percentage of S-phase cells. The treatment of 13-day-old pulmonary nodules with 3 doses of HU also depleted the (G2+M) phase tumour cells and increased the heterogeneity between tumour subpopulations, as determined by FMF analysis.
机译：确定了羟基脲（HU）对作为肺部肿瘤生长的鼠纤维肉瘤（FSa）细胞的体内细胞毒性作用。将来自13天大结节的肿瘤细胞制成悬浮液，并根据细胞大小通过离心淘析进行分离。流动微荧光法（FMF）用于确定细胞周期参数和分离群体的相对同步性，以及每个肿瘤细胞群体中正常二倍体细胞的污染程度。 HU的细胞毒性通过单次1 mg / g i.p.剂量给已经静脉注射的小鼠提前20分钟使用已知数量的同步存活FSa细胞，并进行i.p.剂量为每只1 mg / g的小鼠进入带有13天大的肺结节的小鼠体内。在后一实验中，最后一次给药后1小时将动物处死，切下肿瘤结节，制成单细胞悬液并淘洗。将来自每个级分的已知数量的细胞注射到受体小鼠中以确定存活率。在这两组实验中，被HU杀死的细胞与S期细胞的百分比相关。用FMF分析确定，用3剂量的HU治疗13天大的肺结节，也会耗尽（G2 + M）期肿瘤细胞，并增加肿瘤亚群之间的异质性。

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