吞噬细胞释放的氧自由基和肿瘤坏死因子增加α粒子致细胞转化频率的研究

Enhancement of alpha particles induced cell transformation by oxygen free radicals and tumor necrosis factor released from phagocytes.

阐明慢性炎症时吞噬细胞释出的某些内源性因子在辐射致癌中的作用。方法以Ｃ３Ｈ１０Ｔ１／２和原代ＳＨＥ为靶细胞，用２３８Ｐｕ为体外α照射源，用转化灶形成法观察ＰＭＡ及其刺激人外周血产生的过量自由基、调理酵母多糖刺激Ｕ－９３７细胞释放的ＴＮＦ－α等炎性因子对α粒子照射细胞转化频率（ＴＦ）的增加效应。结果ＰＭＡ和它刺激的人血使０．５Ｇｙα粒子照射的Ｃ３Ｈ１０Ｔ１／２细胞的ＴＦ分别增高２．１和２．８倍。Ｕ－９３７释放的ＴＮＦ－α炎症因子ＴＦ增高１２倍；用抗ＴＮＦ－α抗体中和后，证明Ｕ－９３７上清中仍有其他促癌因子存在。０．５Ｇｙα粒子照射的ＳＨＥ细胞在体外长期传代生长对ｈｒＴＮＦ－α具有依赖性，由此得到的４０代的细胞具有致瘤性。结论慢性炎症条件下，中性粒细胞和巨噬细胞释出的过量自由基和ＴＮＦ－α等因子在低剂量辐射致癌中起重要作用。

Objective To illustrate the role of several endogenous factors released from phagocytes under chronic inflammation in radiation induced cancer.Methods C 3T 10 T 1/2 and SHE cells were used as targets,and 238 Pu alpha source was used in alpha irradiation .The enhancement of TF in alpha particles induced cell transformation by PMA stimulated human blood and zymosan stimulated U 937 cells was studied using formation of transformed foci.Results Transformation frequency (TF) of C 3H 10 T 1/2 cells exposed to alpha particles of 0.5Gy increased 2.1 and 2.8 fold by PMA and PMA stimulated neutrophils,respectively.TF of irradiated SHE cells at a dose of 0.5Gy increased 12 fold by the addition of the supernatant of macrophage like U 937 cell line.It was shown that TF of irradiated SHE cells at above dose increased 8 fold by the supernatant treated with anti TNF α antibody and there were unknown promoters in it.The irradiated SHE cells treated with human recombinant TNF α could be subcultured continuously in vitro.The cells at 40th passage and two lines of monoclone cells have the ability to develop malignant tumors in nude mice.Conclusion The overdose of free radicals and TNF α released from neutrophils and macrophages have played an important role in low dose radiation induced cancer.