The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats.
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.
Hashimoto
S
S
Department of Radiology, Hokkaido University School of Medicine, Sapporo, Japan.
Shirato
H
H
Hosokawa
M
M
Nishioka
T
T
Kuramitsu
Y
Y
Matushita
K
K
Kobayashi
M
M
Miyasaka
K
K
D000818:Animals; D007371:Interferon-gamma / Q000235:genetics; D008297:Male; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014916:Whole-Body Irradiation
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma