EXPERIMENTAL RADIOTHERAPY, CARCINOGENESIS, AND PROTECTOR

本研究的目的是（1）表征 正常和肿瘤组织细胞对电离辐射的反应 和/或选择的化疗剂作为治疗的函数 协议和（2）使用化学改性剂，如辐射防护剂， 阐明导致观察到的 方面的影响. 这项研究将集中在最大限度地提高治疗收益， 最大限度地减少辐射对生产过程的感应影响， 在治疗期间暴露的正常组织中的诱变。 在体外 和体内细胞系统将被用来评估的有效性， 选择的辐射保护剂，包括2-[（氨基丙基）氨基] 乙烯利（WR 1065）和S-2-（3-氨基丙基氨基）乙基硫代磷酸酯 酸（WR 2721）。 将对两种修复进行致突变研究- 熟练（K1，AA 8）和修复缺陷（xrs-5，EM 9）CHO细胞系， 以及用命名为L33的人淋巴母细胞样细胞系， 测定放射和/或药物诱导的突变， 次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）基因座作为一种 辐射防护化学品在这些过程中的作用也将被 测定 用于评估治疗增益的肿瘤系统包括 甲基胆蒽诱导的纤维肉瘤（FSa）， 纤维肉瘤（NFSA）和自发性乳腺癌（MCa- K）。 这些肿瘤将在特定菌群和常规菌群中生长 C3 Hf/Sed小鼠。 DNA损伤和修复将被测量 通过离心淘洗等技术， 分离独特细胞群用于研究。 通过整合 这些系统，将有可能评估的有用性， 化学改性剂，如辐射防护剂， 治疗增益，但也显着降低相关的风险， 正常人照射诱变和致癌作用 组织中

The objectives of this investigation are (1) to characterize the response of cells from normal and tumor tissue to ionizing radiation and/or selected chemotherapeutic agents as a function of therapeutic protocol and (2) to use chemical modifiers such as radioprotectors to elucidate the underlying mechanisms of action leading to the observed effects. This study will focus on maximizing therapeutic gain while minimizing the inductive effects of radiation on the process of mutagenesis in normal tissues exposed during treatment. Both in vitro and in vivo cell systems will be used to assess the effectiveness of selected radioprotectors, which include 2-[(aminopropyl) amino] ethanethiol (WR1065) and S-2-(3-aminopropylamino) ethyl phosphorothioic acid (WR2721). Mutagenesis studies will be performed with both repair- proficient (K1, AA8) and repair-deficient (xrs-5, EM9) CHO cell lines, as well as with a human lymphoblastoid cell line designated L33, by assaying for radiation and/or drug-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus as a function of radioprotector chemicals on these processes will also be determined. Tumor systems to be used to assess therapeutic gain include a methylcholanthrene-induced fibrosarcoma (FSa), a spontaneously arisen fibrosarcoma (NFSA), and a spontaneously arisen mammary carcinoma (MCa- K). These tumors will be grown in both defined-flora and conventionally maintained C3Hf/Sed mice. DNA damage and repair will be measured through the techniques such as centrifugal elutriation will be used to isolate unique cell populations for study. Through the integration of these systems, it will be possible to evaluate the usefulness of chemical modifiers such as radioprotectors to not only improve therapeutic gain but also significantly reduce the associated risk of therapy-induced mutagenesis and carcinogenesis in exposed normal tissues.