Regional thymidine transport and incorporation in experimental brain and subcutaneous tumors.

Regional thymidine transport and incorporation in experimental brain and subcutaneous tumors.
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实验性脑和皮下肿瘤中的区域胸苷转运和掺入。

DOI:
10.1111/j.1471-4159.1984.tb00918.x
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发表时间:
1984
影响因子:
4.7
通讯作者:
Fenstermacher,J
Fenstermacher,J
中科院分区:
医学2区
文献类型:
--
作者:
Molnar,P;Groothuis,D;Blasberg,R;Zaharko,D;Owens,E;Fenstermacher,J

文献摘要

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在正常组织和新塑性组织中测量了[14C]胸腺嘧啶的区域分布和局部并入不可提取的组织部分(可能是DNA)。我们研究了由禽肉瘤病毒和乙基亚硝基脲诱导的脑肿瘤,并移植了RG‐2脑内和皮下胶质瘤。根据组织中甲醇不可提取的放射性和胸苷的血浆浓度-时间积分,计算不同肿瘤区域和大脑的掺入商Q。结合商表示胸腺嘧啶从血液中的清除率及其与大分子(可能是NA)的结合率。将q值与常规放射自显影术在同一组织区域测量的标记指数进行比较。结果如下:(1)胸苷的平均血浆半衰期为6.5 min;(2)肿瘤的区域融合商从与正常大脑相当的值到高于正常大脑100倍以上的值不等;(3) RG‐2肿瘤的q值明显高于其他肿瘤模型;(4)秦皮下肿瘤变异范围最广(约500倍);(5)标记指标反映了部分肿瘤区域的qin值,但在其他区域没有;两者之间的差异最常与肿瘤细胞密度和单个肿瘤细胞标记的强度有关。将这些数据与先前对这些肿瘤模型中毛细血管通透性和血流的研究进行比较表明,[14C]胸腺嘧啶掺入不可提取的组织部分可能受到脑肿瘤的经毛细血管运输和全身肿瘤的血流的限制,并且胸腺嘧啶在这些肿瘤中的配置并不总是表明DNA合成的速度。
The regional distribution and local incorporation of [14C]thymidine into a nonextractable tissue fraction, probably DNA, was measured in normal and neo‐plastic tissues. We studied brain tumors induced by avian sarcoma virus and ethylnitrosourea, and transplanted RG‐2 intracerebral and subcutaneous gliomas. An incorporation quotient,Q, was calculated for different tumor regions and brain from the methanol nonextractable radioactivity in the tissue and the plasma concentration‐time integral of thymidine. The incorporation quotient represents the rate of clearance of thymidine from bloodandits incorporation into macromolecules (probably I NA). The values ofQwere compared with a labeling index measured in the same tissue regions with conventional autoradiography. The following observations were made: (1) the mean plasma half‐life of thymidine was 6.5 min; (2) the regional incorporation quotient in tumors varied from values comparable to normal brain to more than 100 times higher; (3) RG‐2 tumors had significantly higherQs than the other tumor models; (4)Qin subcutaneous tumors varied most widely (>500‐fold range); (5) the labeling index reflected the values ofQin some tumor regions but not in others; differences between the two were most frequently related to tumor cell density and the intensity of individual tumor cell labeling. A comparison of these data with previous studies of capillary permeability and blood flow in these tumor models indicates that the incorporation of [14C]thymidine into a nonextractable tissue fraction can be limited by transcapillary transport in brain tumors and by blood flow in systemic tumors, and that thymidine disposition in these tumors is not always indicative of the rate of DNA synthesis.