DRUG-INDUCED SCES IN HUMAN PRIMARY TUMOR CELL CULTURE

预测单个肿瘤对后续化疗的反应的能力 化疗在癌症治疗中具有明显的临床优势。 我们以前已经证明，对于已建立的肿瘤细胞的治疗， 特异性化疗药物诱导的姐妹染色单体细胞系 SCE与药物诱导的细胞杀伤相关。 的目标 该建议是研究SCE试验作为模型的使用， 预测原代人肿瘤细胞培养物对特异性 吸毒。 这些研究将涉及药物的排名 原代培养物根据其SCE剂量反应的敏感性 或者更重要的是，评估药物的异质性， 肿瘤细胞亚群之间存在的敏感性， SCE频率直方图的生成（细胞数与 SCE/染色体）。 SCE剂量-反应曲线将在 用顺铂、BCNU处理人肿瘤细胞的原代培养物 或美法仑以及SCE预测的相对敏感性， 存活测定比较。 顺铂、BCNU和 存在于原代肿瘤细胞培养物中的美法仑反应将是 通过构建SCE频率直方图进行研究。 毒品- 诱导SCE频率直方图也将用于研究 内在放射反应的肿瘤内多样性。 检测 这种形式的异质性将基于药物的修饰- 诱发SCE频率直方图。 这些拟议 研究应有助于评估SCE分析的潜在应用 作为一种预测性测定，并可能提供对异质性的洞察， 人肿瘤中存在的免疫应答。

The ability to predict the response of an individual tumor to subsequent chemotherapy would offer obvious clinical advantages in cancer treatment. We have previously shown that for the treatment of established tumor cell lines with specific chemotherapeutic agents, drug-induced sister chromatid exchanges (SCEs) are correlated with drug-induced cell kill. The goal of this proposal is to investigate the use of the SCE assay as a model for predicting the response of primary human tumor cell cultures to specific antineoplastic drugs. These studies will involve ranking the drug sensitivities of primary cultures according to their SCE dose-responses and, or probably greater significance, evaluating the heterogeneity in drug sensitivity existing among the tumor cell subpopulation through the generation of SCE frequency histograms (number of cells versus SCEs/chromosomes). SCE dose-response curves will be generated after treatment of primary cultures of human tumor cells with cis-platinum, BCNU or melphalan and the relative sensitivities as predicted by the SCE and a survival assay compared. The heterogeneity in cis-platinum, BCNU and melphalan response existing in primary tumor cell cultures will be investigated through the construction of SCE frequency histograms. Drug- induced SCE frequency histograms will also be used to investigate intraneoplastic diversity in intrinsic radiation response. The detection of this form of heterogeneity will be based on the modification of drug- induced SCE frequency histograms by prior X-irradiation. These proposed studies should aid in evaluating the potential application of SCE analysis as a predictive assay and may provide insight into the heterogeneity in antineoplastic response existing within human tumors.