Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo.
Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo.
复制标题
缺氧的细胞周期分布和体内缺氧肿瘤细胞的进展。
DOI：
10.1038/bjc.1998.38
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发表时间：
1998
影响因子：
8.8
通讯作者：
Wilson, G D
中科院分区：
文献类型：
--
作者：
Webster, L;Hodgkiss, R J;Wilson, G D
通过测量7-（4'-（2-硝基咪唑-1-基）-丁基）-茶碱（NITP）的结合，在体内评估三种小鼠肿瘤模型中的缺氧情况，NITP是一种免疫可识别的缺氧标志物，在低氧条件下与细胞生物还原结合。通过胸腺嘧啶类似物溴脱氧尿苷（BrdUrd）在同一肿瘤中标记增殖细胞。通过添加碘化丙啶和流式细胞术分析，评估肿瘤分离细胞在每个细胞周期阶段的相对缺氧情况。在间变性肉瘤SaF和低分化癌can中，肿瘤体积与缺氧无相关性，而在中度高分化癌Rh中，肿瘤体积与缺氧有轻微的负相关。G1/G0期含有最多的非整倍体缺氧细胞（非整倍体缺氧在SaF、can和Rh中分别从不到1%到40%、38%和71%不等），尽管在所有三个肿瘤的S-期和G2/M期都存在大量的缺氧。然而，缺氧的比例最高发生在G2/M期，其中高达60%的细胞缺氧。采用新颖的三重染色流式细胞术同时测量缺氧、增殖和DNA含量表明，缺氧细胞可以积极参与细胞周期。此外，NITP和BrdUrd标记的细胞周期分布表明，缺氧细胞可以通过细胞周期，尽管其进展速度比良好氧合细胞慢。
Hypoxia was assessed in three murine tumour models in vivo by measuring the incorporation of 7-(4'-(2-nitroimidazole-1-yl)-butyl)-theophylline (NITP), an immunologically identifiable hypoxia marker that binds bioreductively to cells under low-oxygen conditions. Proliferating cells were labelled in the same tumours by administering the thymidine analogue bromodeoxyuridine (BrdUrd). The relative hypoxia in each cell cycle phase of cells isolated from tumours was assessed by addition of propidium iodide with analysis by flow cytometry. There was no relationship between tumour volume and hypoxia in either the anaplastic sarcoma SaF or the poorly differentiated carcinoma CaNT and only a slight negative correlation in moderately well-differentiated carcinoma Rh. The G1/G0 phase contained the greatest number of aneuploid hypoxic cells (aneuploid hypoxia ranging from less than 1% up to 40%, 38% and 71% in SaF, CaNT and Rh respectively), although there were significant amounts of hypoxia present in S- and G2/M phases for all three tumours examined. However, the highest proportion of hypoxia occurred in the G2/M phase, in which up to 60% of the cells were hypoxic. Simultaneous measurement of hypoxia, proliferation and DNA content using a novel triple-staining flow cytometry method showed that hypoxic cells could actively participate in the cell cycle. In addition, the cell cycle distribution of NITP and BrdUrd labelling showed that hypoxic cells could progress through the cell cycle, although their rate of progression was slower than that of better oxygenated cells.