DRUG-INDUCED SCES IN HUMAN PRIMARY TUMOR CELL CULTURE

预测单个肿瘤对后续治疗的反应的能力 化疗在癌症治疗中具有明显的临床优势。 我们之前已经证明，对于已建立的肿瘤细胞的治疗 具有特定化疗药物、药物诱导的姐妹染色单体的品系 交换(SCE)与药物诱导的细胞杀伤相关。的目标是 这项建议是为了调查姐妹染色单体交换试验作为模型的使用 预测原代培养的人肿瘤细胞对特异性抗体的反应 抗肿瘤药物。这些研究将涉及对药物进行排名 原代培养物对姐妹染色单体交换剂量反应的敏感性 以及，或者可能更重要的是，评估药物的异质性 肿瘤细胞亚群中存在的敏感性通过 产生姐妹染色单体交换频率直方图(细胞数与 SCES/染色体)。SCE剂量-反应曲线将在以下时间后生成 顺铂、BCNU对原代培养的人肿瘤细胞的作用 或马法兰，以及由姐妹染色单体交换委员会和一个 比较存活试验结果。顺铂、顺铂和顺铂的异质性 在原代肿瘤细胞培养中存在的马法兰反应将是 通过构建姐妹染色单体交换频率直方图进行研究。毒品-- 诱发的姐妹染色单体交换频率直方图也将用于研究 本征辐射反应中的肿瘤内多样性。该检测 这种形式的异质性将基于药物的修饰- X射线照射诱导的姐妹染色单体交换频率直方图。这些建议 研究应有助于评估姐妹染色单体交换分析的潜在应用 作为一种预测性分析，并可能提供对 存在于人类肿瘤内的抗肿瘤反应。

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.