EXPERIMENTAL RADIOTHERAPY, CARCINOGENESIS, AND PROTECTOR

本次调查的目的是(1)确定 正常组织和肿瘤组织细胞对电离辐射的反应 和/或选定的化疗药物作为治疗的功能 议定书和(2)使用化学修饰剂，如辐射防护剂 阐明导致观察到的 效果。这项研究将集中在最大化治疗收益的同时 最大限度地减少辐射对过程的诱导效应 在治疗过程中暴露的正常组织的诱变。两者都在体外 体内细胞系统将被用来评估 选定的辐射防护剂，包括2-[(氨丙基)氨基] 乙硫醇(WR1065)和S-2-(3-氨基丙氨基)乙基硫代磷 酸(WR2721)。突变研究将在修复的同时进行- 精通(K1，aa8)和修复缺陷(XRS-5，EM9)CHO细胞系， 以及命名为L33的人类淋巴母细胞系，通过 检测辐射和/或药物引起的突变 次黄嘌呤-鸟嘌呤磷酸核糖基转移酶(HGPRT)基因座作为 辐射防护剂对这些过程的作用也将是 下定决心。用于评估治疗收益的肿瘤系统包括 自发性甲基胆汁性纤维肉瘤(FSA) 纤维肉瘤(NFSA)和自发性乳腺癌(MCA- k)。这些肿瘤将在限定的菌群和常规的菌群中生长。 维持C3Hf/SED小鼠。DNA损伤和修复将被测量 通过离心淘洗等技术将被用来 分离独特的细胞群体以供研究。通过整合 这些系统，将有可能评估的有用性 化学修饰剂，如辐射防护剂，不仅可以改善 但也显著降低了相关的风险 暴露于正常人群的治疗诱变和致癌作用 纸巾。

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.