BIOLOGICAL ASPECTS OF CARCINOGENESIS BY RADIATION

辐射致癌的生物学方面

• 批准号: 3163142
• 负责人: JOHN MARTIN BROWN
• 金额: $ 43.43万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 1989-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163142
• 关键词: Gross' virus; Rauscher's virus; Retroviridae disease; T lymphocyte; X ray; cell free system; cell sorting; chemical carcinogenesis; clone cells; cytogenetics; electron microscopy; embryo /fetus; gene expression; genetic manipulation; immunofluorescence technique; immunogenetics; ionizing radiation; lymphoma; microinjections; molecular cloning; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; nucleic acid sequence; oncogenic virus; radiation genetics; radiation leukemia; radiotracer; relative biological effectiveness; temperature sensitive mutant; thymus; thymus neoplasms; viral leukemogenesis; virus antigen; virus cytopathogenic effect; virus genetics; virus replication

We wish to continue our studies of the induction of thymic T-cell lymphomas in mice exposed to ionizing radiation or to chemical leukemogens. Specifically, we plan to investigate: 1. the contribution of lymphostromal and lymphoepithelial multicellular complexes to the thymus microenvironment essential for murine T-cell lymphomagenesis. 2. the role of natural killer (NK) cells and other mechanisms of immune surveillance in lymphomagenesis. 3. the hypothesis that viral envelope antigens induce autostimulatory blastogenesis leading to tumor development. 4. the evolution of autonomy of such lymphomas as related to phenotypic markers and chromosome numbers. 5. the hypothesis that radiation or chemicals activate an oncogenic replication-defective "xenotropic-like" retroviral genome which then induces apparently virus-negative lymphomas. 6. the hypothesis that lymphomagenic, replication-competent retrovirus may later be generated when such lymphomas are infected by a sporadically expressed non-oncogenic ecotropic virus, leading to "rescue' of the replication-defective "xenotropic-like" oncogenic genome. 7. the "promoter insertion" hypothesis and other possible molecular mechanisms of murine retroviral lymphomagenesis.

我们希望继续研究胸腺T细胞淋巴瘤 在暴露于电离辐射或化学白血病的小鼠中。 具体来说，我们计划调查： 1。淋巴细胞和淋巴皮多细胞的贡献 对鼠T细胞必不可少的胸腺微环境的复合物 淋巴作用。 2。自然杀手（NK）细胞的作用和免疫的其他机制 淋巴作用中的监测。 3。病毒包膜抗原诱导自动刺激的假设 囊泡发生导致肿瘤发育。 4。与表型相关的淋巴瘤自主的演变 标记和染色体数。 5。辐射或化学物质激活致癌的假设 复制缺陷的“异形样”逆转录病毒基因组，然后 诱导病毒阴性淋巴瘤。 6。假设淋巴瘤，复制能力逆转录病毒可能 稍后，当这种淋巴瘤偶发地感染此类淋巴瘤时会产生 表达了非癌性生态病毒，导致“营救” 复制缺陷的“异形样”致癌基因组。 7。“启动子插入”假设和其他可能的分子 鼠逆转录病毒淋巴作用的机理。