【摘要】 <正> 在发展新的半合成蒽环类抗癌抗生素的研制过程中,试用了新近在四川省肿瘤研究所建立的“人体肿瘤材料筛选系统”(HTMSS,Human Tumor Materials Sereening System)——包括人DNA,人癌细胞,人体肿瘤组织三级筛选:1.体外HDI系统(Human DNA Interaction System.):首先从分子水平上提供抗癌筛选信息,快速考察新衍生物与人癌细胞DNA的作用效应及模式,与已知抗癌药物相比较。2.细胞培养试验,运用细胞集落形成能力试验(ColonyFormation Assay,CFA),大分子物质合成试验(Macromolecular Synthesis),DNA转化试验(DNA Transfer Method),骨髓细胞毒性试验,细胞免疫功能试验等方法,从更多还原

【Abstract】 Anthracyclines is an important antitumor antibiotics family, which including adriamycin, daunorubicin, carcinomycin and aclacinomycin etc clinically effective antibiotics. The development of new semi-synthesized anthracyclines to get lower toxicity and high activity is still an attractive project in the cancer chemotherapy field.For the screening of new antitumor agents, a new Human Tumor Materials ScreeningSystem (HTMS) has been established in Sichuan Institute for Cancer Research recently.-which including three screening stepst human DNA, human cell culture and human tumor tissue xenograft. 1. in vitro HDI (Human DNA Interaction) system: Using this cell-free system to investigate the mode of action and the HDI activity informations of new antitu- mor compounds. 2. Human tumor (or normal) cell culture: A variety of cell culture methods is available to examine the transport capability, the cell toxicity and mechanism of action of new antitumor agents, for example: CFA (Colony Formation Assay), MSE (Macro -molecular Synthesis Experiment), NC-DT(Normal Cells-DNA Transfection method) ,GM-CFU (Granulocyte-Macrophage Colony-Forming Units)etc. 3. in vivo human tumor xenograft animal test:Using the transplantationestablished human tumor xenograft in the athymic mouse, immune-deprived mouse, or SRC (Subrenal Capsule Assay) in the normal immune-compa tent mouse,to examine the in vivo responses of cancer chemotherapy with new antitumor agents.Here we report the screening of 14 new semi-synthesized anthracyclines by HDI system and human tumor cells CFA method.For studying the different types of antitumor drugs, HDI system contains several patterns: DNA strand scission pattern, Intercalation reversion pattern, Cross-linking pattern etc. The HDI intercalation reversion pattern was selected for the screening of anthracyclines. The comparative HDI intercalation reversion patterns of 14 new anthracyclines with adriamycin and daunorubicin as the standards were demonstrated. There were 6 from them. Showed Potent intercalation with human tumor cellular DNA, both the reversible intercalation and irreversible intercalation were stronger than daunorubicin, but similar to adriamycin. (A1026, A1028,Al029, AlOSl, Ai040, Ai041).A human gastric carcinoma cell line SGC-7901 has been used for the CFA of these new anthracyclines. Their ICF50(the drug dose of 50% Inhibition of Colony Formation)were compared: A1028---0.024μg/ml, A1026---0.047μg/ml, Al041---0.047μg/ml, and ADR------<0.01/μg/ml.From these screening tests, we would recommend Al028 & A1041, A1026. these 3 new anthracyclines for the further antitumor experimental studies.The theoretical basis and practical value of this new screening system is discussed.更多还原