EFFECTS OF RADIATION ON NORMAL-TISSUES - HYPOTHETICAL MECHANISMS AND LIMITATIONS OF INSITU ASSAYS OF CLONOGENICITY

EFFECTS OF RADIATION ON NORMAL-TISSUES - HYPOTHETICAL MECHANISMS AND LIMITATIONS OF INSITU ASSAYS OF CLONOGENICITY
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DOI:
10.1007/bf01324183
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发表时间:
1981-01-01
影响因子:
1.7
通讯作者:
MICHALOWSKI, A
MICHALOWSKI, A
中科院分区:
环境科学与生态学4区
文献类型:
--
作者:
MICHALOWSKI, A

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据认为,增殖正常组织分为两类。在H型组织中,细胞要么增殖,要么执行组织特异性功能。灭菌剂量的辐射立即引起不可逆的有丝分裂后成熟细胞的逐渐减少。功能性细胞消耗的恒定速率由细胞的生理寿命给出。因此,最大数量减少的开始与剂量无关,在一系列辐射剂量之后,较轻损害的峰值比较严重损害的峰值更早出现。在F型(柔性)组织中,所有细胞都被认为具有增殖潜力,并且还参与组织特异性功能。辐射通过有丝分裂死亡导致功能细胞的剂量依赖性损失,无论是在暴露后立即还是在下一阶段增加的补偿性增殖期间,导致辐射损伤的加速表达(“雪崩”)。因此,大剂量辐射后出现的更严重的损伤比小剂量辐射产生的更轻微的损伤要早。体内细胞克隆形成性的测定几乎只涉及H型群体。在这些测定中施用的大辐射/药物/热剂量用于将克隆形成细胞稀释至少两个数量级,并产生可测量的反应。当比较两种药物或解释其联合作用时,建议确保稀释步骤产生的克隆形成细胞样品在质量上相当,然后根据剂量-存活曲线参数进行表征。
It is argued that proliferating normal tissues fall into two categories. In type H (for hierarchical) tissues, cells either multiply or perform tissue-specific functions. Sterilizing doses of radiation immediately initiate a gradual depopulation of irreversibly postmitotic, mature cells. The constant rate of functional cell depletion is given by physiological longevity of the cells. Consequently the onset of maximal depopulation is dose-independent and, after a range of radiation doses, the peak of milder damage is seen earlier than that of a more severe one. In type F (for flexible) tissues all cells are assumed to have the potential for proliferation and are also engaged in tissue-specific functions. Radiation leads to dose-dependent loss of the functional cells through their mitotic death, both immediately after exposure and during the next phase of increased compensatory proliferation resulting in accelerated expression of radiation damage (‘avalanche’). Consequently the more severe damage following larger doses of radiation is seen earlier than the milder one produced with smaller doses.Assays of cell clonogenicity in vivo concern almost exclusively type H populations. The large radiation/drug/heat doses administered in these assays serve both to dilute the clonogenic cells by at least two orders of magnitude, and to produce a measurable response. When comparing two agents or interpreting their combined action it is advisable to ensure that the dilution step yields qualitatively comparable samples of clonogenic cells to be then characterized in terms of dose-survival curve parameters.