FLOW CYTOMETRIC STUDY OF ANTICANCER DRUG EFFECTS ON DNA

本研究的总体目标是实验和临床研究。 DNA损伤检测在单个细胞检测中的应用 用抗DNA单抗进行细胞染色。流式细胞仪 烷化剂对细胞DNA损伤的测定 被证明可以评估异质细胞群体中的耐药性， 分析DNA修复并筛选有治疗作用的DNA修复 抑制剂。DNA修复及其化疗药物的抑制作用 将研究开发高效维修的筛查系统 抑制剂及合理的联合化疗基础 基于DNA修复抑制。不同类型药物的药效 辐射诱导的DNA损伤修复的分类及其组合 代表主要肿瘤定位的细胞系中的烷化剂 将会被研究。临床应用的目标是开发 卵巢癌、多发性骨髓瘤、慢性卵巢癌的药敏试验 髓系白血病和慢性淋巴细胞性白血病。实体瘤将会是 在体外用烷化剂处理，分解和DNA损伤 将在非整倍体肿瘤细胞中进行测量。从血液中分离的细胞 骨髓将用烷化剂和DNA损伤进行治疗 将在流式细胞仪上进行测量。DNA损伤的强度 将体外药物诱导的反应与患者的反应进行比较 用烷化剂进行化疗。DNA修复的作用 烷基化药物对卵巢肿瘤DNA损伤的抑制作用 将在体外进行研究，以确定其敏感性 个别肿瘤对DNA修复有抑制作用。人的DNA修复率 白血病细胞将通过DNA免疫反应性下降来评估 在无药物培养液中孵育期间。修复率将是 与抗药性的发展密切相关。细胞的作用 在耐药性形成过程中的相互作用将在 人类肿瘤的细胞培养和异种移植。药品筛选系统 它基于细胞亚群与细胞的相互作用来消除阻力 不同的抗性机制将被开发出来。

The general goal of this study is the experimental and clinical applications of DNA damage assay in individual cells based on the staining of cells with anti-DNA monoclonal antibody. Flow cytometric measurements of DNA damage in the cells treated with alkylating agents was shown to evaluate drug resistance in heterogeneous cell populations, to analyze DNA repair and to select therapeutically useful DNA repair inhibitors. DNA repair and its inhibition by chemotherapeutic agents will be studied to develop screening system for efficient repair inhibitors and to develop rational basis for combination chemotherapy based on DNA repair inhibition. The effects of drugs of different classes and their combinations of the repair of DNA damage induced by alkylating agents in cell lines representing major tumor localizations will be studied. The goal of clinical applications is to develop chemosensitivity tests for ovarian carcinomas, multiple myeloma, chronic myeloid leukemia and chronic lymphoid leukemia. Solid tumors will be treated in vitro with alkylating agents, disaggregated and DNA damage will be measured in aneuploid tumors cells. Cells isolated from blood and bone marrow will be treated with alkylating agents and DNA damage will be measured on a flow-cytometer. The intensity of DNA damage induced by drugs in vitro will be compared with the response of patients to chemotherapy with alkylating agents. The effect of DNA repair inhibitors on DNA damage induced by alkylating agents in ovarian tumors in vitro will be studied in order to determine the sensitivity of individual tumors to DNA repair inhibition. The rate of DNA repair in leukemic cells will be evaluated by decrease of DNA immunoreactivity during post-incubation in drug-free medium. Rate of repair will be correlated with the development of resistance. The role of cell interaction in the development of drug resistance will be studied in cell culture and xenografts of human tumors. Screening system for drugs which eliminate resistance based on interaction of cell subsets with different mechanisms of resistance will be developed.