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体内对每一个克隆源性大鼠乳腺细胞的辐射致癌起始频率的评估。

Assessment of radiogenic cancer initiation frequency per clonogenic rat mammary cell in vivo.

作者信息

Clifton K H, Tanner M A, Gould M N

出版信息

Cancer Res. 1986 May;46(5):2390-5.

PMID:3697982
Abstract

Radiogenic initiation of mammary cancer is here shown to be a common cellular event. With the aid of a rat mammary clonogen transplant system designed to maximize progression of initiated cells to overt neoplasia, the estimated absolute cancer risk per surviving 7 Gy-irradiated mammary clonogen was [4.1 +/- 1.2 (SE)] X 10(-3), that is (5.8 +/- 1.7) X 10(-4) initiated cells per clonogen-Gy. To maximize neoplastic progression, all clonogen graft recipient rats were glucocorticoid deficient (adrenalectomized with minimal mineralocorticoid replacement) and hyperprolactinemic (implanted intrasplenically with pituitary tissue and an estrone capsule). Each rat was grafted with 4 X 10(6) "morphologically intact" monodispersed mammary cells in the interscapular white fat pad. Group A received cells which had been irradiated 1 day earlier with 7 Gy 137Cs gamma-rays. Groups B and C received unirradiated mammary cells. On day 35 after transplantation, the graft sites of group B were locally exposed to 7 Gy 140 kVp X-rays. Kaplan-Meier estimates (11) of the survivor functions were used to calculate the final tumor incidences corrected for intercurrent animal loss. Estimated mammary carcinoma frequencies so calculated were 65 tumors/131 graft sites in group A, 93/119 in group B, and 13/129 in group C. The relative cancer risks per rat due to the radiation exposure of the grafted cells were 5.0 for group A and 7.8 for group B. These data on neoplasia incidence in grafted mammary clonogens and data on autologous neoplasia in the host rat mammary glands were subjected to statistical analysis. The results indicate that both neoplasm frequency and latency are in large part dependent on initiation target cell number. The high frequency of radiogenic initiation per mammary clonogen observed in this study is in accord with findings with a similar thyroid clonogen transplant system.

摘要

本文显示,放射性引发乳腺癌是一种常见的细胞事件。借助一种大鼠乳腺克隆原移植系统,该系统旨在使引发细胞向明显肿瘤的进展最大化,每存活的经7 Gy照射的乳腺克隆原的估计绝对癌症风险为[4.1±1.2(标准误)]×10⁻³,即每克隆原 - Gy有(5.8±1.7)×10⁻⁴个引发细胞。为使肿瘤进展最大化,所有克隆原移植受体大鼠均糖皮质激素缺乏(肾上腺切除并给予最低限度的盐皮质激素替代)且高催乳素血症(经脾内植入垂体组织和一个雌酮胶囊)。每只大鼠在肩胛间白色脂肪垫植入4×10⁶个“形态完整”的单分散乳腺细胞。A组接受1天前经7 Gy ¹³⁷Csγ射线照射的细胞。B组和C组接受未照射的乳腺细胞。移植后第35天,B组的移植部位局部接受7 Gy 140 kVp X射线照射。采用Kaplan - Meier估计法(11)计算生存函数,以校正同期动物死亡后的最终肿瘤发生率。如此计算得出的估计乳腺癌频率为:A组131个移植部位中有65个肿瘤,B组119个中有93个,C组129个中有13个。移植细胞辐射暴露导致的每组大鼠相对癌症风险,A组为5.0,B组为7.8。对移植乳腺克隆原中的肿瘤发生率数据以及宿主大鼠乳腺中的自体肿瘤数据进行了统计分析。结果表明,肿瘤频率和潜伏期在很大程度上取决于引发靶细胞数量。本研究中观察到的每个乳腺克隆原的高放射性引发频率与类似的甲状腺克隆原移植系统的研究结果一致。

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