Caspase cascades which activated by ionizing irradiation

1.人正常和肿瘤细胞系的辐射抗性：10 Gy γ射线照射后，检测人正常细胞（MRC 5）和人肿瘤细胞（HL 60、MGF 7）caspase-8和caspase-9的酶活性。HL 60表达大量的活化的半胱天冬酶，而MRC 5仅显示少量的活化的半胱天冬酶-9（未检测到活化的半胱天冬酶-8）。我们的结论是辐射抗性与caspase的活性有很好的对应关系.我们发现，照射后的MRC 5衍生的条件培养基中含有大量的化学引诱物。北方印迹和抗HGF抗体的竞争活性表明这些化学引诱物之一是HGF。电离辐射诱导的基因表达（DNA阵列分析）我们对辐射的MRC 5进行了DNA分析。bcl-2相关基因表达无明显变化。我们发现caspase-2，-6和10的上调。我们还发现了凋亡抑制基因的上调。我们的结论是，这些上调的抗凋亡蛋白可以解释正常结缔组织的辐射抗性。

1. Radiation resistance of human normal and tumor cell lines.An enzymatic activities of caspase-8 and caspase-9 of human normal (MRC5) and tumor (HL60, MGF7) were analyzed after 10Gy gamma-irradiation. HL60 expressed a significant amount of activated caspases, whereas MRC5 showed only a few amount of active caspase-9 (no active caspase-8 was detected). We concluded that radiation resistance and an amount of active caspase were well corresponding.2. A conditioned medium from irradiated MRC5 contained elevated amount of chemoattractants.We found that irradiated MRC5 derived conditioned medium contained increased amount of chemoattractants. Northern blotting and competitive activity of anti-HGF antibodies indicate that one of these chemoattractants is HGF.3. Ionizing radiation induced gene expression (DNA array analysis)We performed DNA analysis for irradiated MRC5. There were no significant changes in bcl-2 related genes. We found the up-regulation of caspase-2,-6 and 10. We also found the up-regulation of apoptosis suppressing genes. We concluded that these up-regulation of anti-apoptotic proteins may explain the radiation resistance of normal connective tissue.