Repopulation of gamma-irradiated Lewis lung carcinoma by malignant cells and host macrophage progenitors.

Repopulation of gamma-irradiated Lewis lung carcinoma by malignant cells and host macrophage progenitors.
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DOI:
10.1038/bjc.1978.252
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发表时间:
1978-11
影响因子:
8.8
通讯作者:
Peacock, J H
Peacock, J H
中科院分区:
医学1区
文献类型:
--
作者:
Stephens, T C;Currie, G A;Peacock, J H

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使用体外软琼脂集落测定法进行连续细胞存活估计,研究了60Co伽玛射线照射Lewis癌的细胞再生。在局部照射(15- 35 Gy)后,可观察到两种不同类型的菌落:细胞紧密堆积的致密菌落和细胞广泛分散的弥漫性菌落。体外最大的弥漫性菌落形成只有在同时存在足够数量的致密菌落的情况下才能获得。全身照射后只观察到致密菌落。紧凑菌落计数的单细胞存活数据与肺菌落试验估计的细胞存活相关,我们得出结论,紧凑菌落是由克隆源性肿瘤细胞产生的。细胞化学和免疫学证据表明,弥漫性菌落由巨噬细胞组成。局部照射后,克隆源性肿瘤细胞的初始杀伤是剂量依赖性的。在每个剂量水平下,重新种群立即开始,并以大约1天的加倍时间进行。每个肿瘤的巨噬细胞集落形成细胞(巨噬细胞祖细胞)最初减少了约30年,但在2天内迅速恢复到预处理水平。我们得出结论,Lewis肺癌中至少存在两种克隆原细胞群,一种是通过原位增殖重新填充辐照肿瘤的肿瘤细胞,另一种是通过浸润重新填充局部辐照肿瘤的宿主巨噬细胞祖细胞。强调了在体外测定系统中混淆宿主和肿瘤细胞菌落的危害。
Cellular repopulation in Lewis carcinoma irradiated with 60Co gamma-rays was examined by performing sequential cell-survival estimations using an in vitro soft-agar-colony assay. Following local irradiation (15--35 Gy) two distinct types of colony were seen: compact colonies with tightly packed cells and diffuse colonies with widely dispersed cells. Maximal diffuse colony formation in vitro was only obtained in the simultaneous presence of adequate numbers of compact colonies. After whole-body irradiation only compact colonies were observed. Only-cell survival data from compact colony counts correlated with cell survival estimated by the lung colony assay and we conclude that compact colonies are produced by clonogenic tumour cells. Cytochemical and immunological evidence showed that diffuse colonies were composed of macrophages. After local irradiation the initial kill of clonogenic tumour cells was dose dependent. At each dose level, repopulation began immediately and proceeded with a doubling time of about 1 day. Macrophage colony-forming cells (macrophage progenitors) per tumour were initially reduced by about 3 decades, but recovered very rapidly to reach pretreatment levels within 2 days. We conclude that at least two populations of clonogenic cells are present in Lewis lung carcinoma, tumour cells that repopulate irradiated tumours by in situ proliferation and host-macrophage progenitors that repopulate locally irradiated tumours by infiltration. The hazards of confusing host and tumour cell colonies in in vitro assay systems are stressed.