Relationship of hypoxia to metallothionein expression in murine tumors
Relationship of hypoxia to metallothionein expression in murine tumors
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DOI：
10.1016/s0360-3016(98)00329-0
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发表时间：
1998-11-01
影响因子：
7
通讯作者：
Horsman, MR
中科院分区：
文献类型：
--
作者：
Raleigh, JA;Chou, SC;Horsman, MR
目的：为了调查，如果金属硫蛋白，内源性化学和放射保护剂，在小鼠C3H乳腺癌中的缺氧细胞中表达，如果这种表达响应于急性变化，在肿瘤hypoxia.Methods和材料：C3H乳腺肿瘤建立在后腿的雌性CDF，小鼠。然后对小鼠进行空气呼吸（慢性缺氧）、碳源呼吸（缺氧急性减少）或肼苯哒嗪注射（缺氧急性增加）。在实验开始后90分钟，切除肿瘤，在福尔马林中固定，并切片，通过图像分析定量低分化细胞和含金属硫蛋白的细胞。盐酸吡莫硝唑和IgG，小鼠单克隆抗体被用来检测缺氧，和小鼠抗金属硫蛋白单克隆抗体（DAKO）被用来检测I型和II型金属硫蛋白在组的连续tissues.Results：金属硫蛋白的免疫染色强度的分布是相同的，在所有三个组的缺氧细胞和轻的其他地区的肿瘤。肼苯哒嗪注射引起的缺氧急性增加伴随着金属硫蛋白表达的增加（p = 0.04），Carbogen呼吸在很大程度上消除了pimonidazole结合，但金属硫蛋白表达持续在肿瘤的Carbogen呼吸mice.Conclusions：C3H乳腺癌中的低分化细胞强烈表达金属硫蛋白。金属硫蛋白表达对肼苯哒嗪注射引起的缺氧急性增加有反应。肼苯哒嗪在增强生物还原性细胞毒素的活化中的有效性可能被金属硫蛋白的表达增加所抵消。金属硫蛋白在碳源呼吸小鼠的肿瘤中的持续存在可能有助于肿瘤中的残余放射抗性。
Purpose: To investigate if metallothionein, an endogenous chemo- and radioprotectant, is expressed in hypoxic cells in mouse C3H mammary carcinomas and if that expression responds to acute changes in tumor hypoxia.Methods and Materials: C3H mammary tumors were established in the hind legs of female CDF, mice. The mice were then subjected to air breathing (chronic hypoxia), carbogen breathing (acute decrease in hypoxia), or hydralazine injection (acute increase in hypoxia). Ninety nainutes after the start of the experiment, tumors were excised, fixed in formalin, and sectioned, Hypoxic cells and metallothionein-containing cells were quantitated by image analysis. Pimonidazole hydrochloride and an IgG, mouse monoclonal antibody were used to detect hypoxia, and a mouse antimetallothionein monoclonal antibody (DAKO) was used to detect Type I and II metallothionein in sets of contiguous tissue sections.Results: The distribution of immunostaining intensity for metallothionein was the same in all three groups-heavy in hypoxic cells and light in other regions of the tumors. The acute increase in hypoxia caused by hydralazine injection was accompanied by an increase in metallothionein expression (p = 0.04), Carbogen breathing largely eliminated pimonidazole binding, but metallothionein expression persisted in the tumors of carbogen-breathing mice.Conclusions: Hypoxic cells in C3H mammary carcinomas strongly express metallothionein. Metallothionein expression is responsive to acute increases in hypoxia brought about by hydralazine injection. The effectiveness of hydralazine in enhancing the activation of bioreductive cytotoxins might be offset by the increased expression of metallothionein, The persistence of metallothionein in tumors of carbogen-breathing mice might contribute to a residual radioresistance in the tumors, (C) 1998 Elsevier Science Inc.