Ribonuclease inhibitor(RI) is an acidic cytoplasmic glycoprotein with a 50 kDa estimated molecular weight. RI can inhibit the activity of ribonuclease A(RNase A) , whose Ki with RI is 4.0x10-14M, and protect RNA from hydrolysis. Studies of the function of RI were from the hypothesis that it can modulate the metabolism of cytoplasmic RNA. But considering the fact that RI can not inhibit all forms of RNase, so the hypothesis couldn't explain all the roles of RI. Another role of RI is the regulation of angiogenin(Ang.), it can form an tight complex with Ang. and then block its activity.Ang is produced and secreted by tumor cells and normal cells and its molecular mass is 14.4 kDa. It has a robust capacity to induce blood vessel formation in vivo and in vitro. It is expressed widely in many kinds of cell and tissue, such as cultured human colon cancer cells and hepatic cells, gastric cancer, colonic cancer, mammary cancer, carcinoma of corpus uteri and so on. It also exits in normal tissues and cells, such as plasm, renal cells, epithelial cells, smooth muscle cells, blood vessle epithelial cells, fibroblasts and so on. The wide expression of Ang suggests that it is restrictive! y controlled in the body. On the basis of analysis of cDNA sequence, Ang is 35% identical with human pancreatic RNase. Ang forms more restricted complex (Ki=7.1 X 10-16) with RI than that formed by RI and RNase A. X-ray analysis showed that Ang had a very similia space structure. They can both form tight complex with RI. Because RI can form the tight complex with Ang, so it can inhibit the activity of AngMany studies demonstrated that angiogensis, the growth of new vessculature, is an absolut requirement for the maintenance and progression of overwhelming majority of solid tumors. And exogenous restrictions on angiogenesis severely impair tumor growth and sometimes lead to a complete regression. So the hypothesis that blocking angiogenesis could be a strategy to halt tumor growth came from the pioneering studiesof Folkman. Nowadays, many angiogenetic inhibitors have been found, but one shortage of these inhibitors is that only relatively hight concertration can inhibit tumor growth effectively. But the complicated purification process limits their clinical application. Gene therapy can resolve this question in certain degree. Gene therapy is the treatment process that exogenous gene is introduced into target cells and expressed in the body for a long time and then the introduced gene functions in the body. Hematopoietic cells have several advantages as target cell for gene therapy: (1)It is easy to be collected from patient autografly or from cord blood cells. Current studies show that cord blood is rich of hematopoietic stem cells and progenitor cells. And the content of hematopoietic stem cells and progenitor cells, which have strong capacity of proliferation, is high. The graft versus host disease(GVHD) is slight. It is a favorable target cell for gene therapy. (2)Its capacity of self-renewing is attractive for long term and resistant expression of the interested gene. (3)Easy to be cultured. (4)Easy to be transplanted into patient's body and survive.Our research group have explored many studies about the anti-tumor activity of RI We purified RI from human placenta and porcine liver. And our recent investigation showed that exogenous ribonuclease inhibitor can inhibit the growth of mice tumors, including Ca761, S180, H22 solid tumor. Our experiments also demonstrated a reduced activity of RI in the blood of tumor patients and a significantly lower level of mRNA in the breast cancer tissue than that in normal tissue.The purpose of this study is to introduce human ribonuclease inhibitor gene into mice bone marrow hematopoietic cells using retrovirus vector system and induce its high expression in cell. Further investigation is to transplant the infected bone marrow cells into v -ray radiated miqe and hope ri gene can be expressed for a long time in the body of mice and the expressed RI can inhibit the growth of melanoma impla