Hashimoto S, Shirato H, Hosokawa M, Nishioka T, Kuramitsu Y, Matushita K, Kobayashi M, Miyasaka K
Department of Radiology, Hokkaido University School of Medicine, Sapporo, Japan.
Radiat Res. 1999 Jun;151(6):717-24.
We have shown that metastasis is suppressed by low-dose total-body irradiation (TBI) in tumor-bearing rats. We have evaluated the immunological effects of low-dose TBI. Total-body irradiation with 0.2 Gy was given 14 days after the implantation of 5 x 10(5) allogenic hepatoma cells (KDH-8) which produce transforming growth factor beta (TGF-beta). On day 21, the splenocytes and tumor-tissue infiltrating lymphocytes were analyzed by FACScan and RT-PCR for the mRNA of the genes that encode tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), TGF-beta, interleukin (IL)-4, IL-10 and IL-6. The same procedure was conducted with untreated rats and with rats that underwent local irradiation with 0.2 Gy. The low-dose TBI significantly decreased the incidence of lung and lymph node metastasis (P < 0.01), whereas the same dose of local irradiation had no effect on the incidence of metastasis. The proportion of CD8+ cells in splenocytes increased in the low-dose TBI group (P < 0.01) compared to the locally irradiated and the untreated groups. The tumor-tissue infiltrating lymphocytes were also significantly increased after low-dose TBI (P < 0.01). The FACScan analysis revealed that 72% of the tumor-tissue infiltrating lymphocytes were CD8+. In both spleen and tumor tissue after low-dose TBI, mRNA expression of the genes that encode IFN-gamma and TNF-alpha increased, while that of the Tgfb gene decreased. There was no expression of the mRNAs of the Il4, Il6 and Il10 genes. CD8+ cells and the cytokine network may play an important role in the antitumor effect of low-dose TBI.
我们已经表明，低剂量全身照射（TBI）可抑制荷瘤大鼠的转移。我们评估了低剂量TBI的免疫效应。在植入5×10⁵个产生转化生长因子β（TGF-β）的同种异体肝癌细胞（KDH-8）14天后，给予0.2 Gy的全身照射。在第21天，通过流式细胞仪（FACScan）和逆转录聚合酶链反应（RT-PCR）分析脾细胞和肿瘤组织浸润淋巴细胞中编码肿瘤坏死因子α（TNF-α）、干扰素γ（IFN-γ）、TGF-β、白细胞介素（IL）-4、IL-10和IL-6的基因的mRNA。对未处理的大鼠和接受0.2 Gy局部照射的大鼠进行相同的操作。低剂量TBI显著降低了肺和淋巴结转移的发生率（P<0.01），而相同剂量的局部照射对转移发生率没有影响。与局部照射组和未处理组相比，低剂量TBI组脾细胞中CD8⁺细胞的比例增加（P<0.01）。低剂量TBI后肿瘤组织浸润淋巴细胞也显著增加（P<0.01）。流式细胞仪分析显示，72%的肿瘤组织浸润淋巴细胞为CD8⁺。在低剂量TBI后的脾脏和肿瘤组织中，编码IFN-γ和TNF-α的基因的mRNA表达增加，而Tgfb基因的表达降低。Il4、Il6和Il10基因的mRNA没有表达。CD8⁺细胞和细胞因子网络可能在低剂量TBI的抗肿瘤作用中发挥重要作用。
