RADIOBIOLOGY OF LETHALITY, MUTATION, & TRANSFORMATION

致死性、突变的放射生物学

• 批准号: 3479697
• 负责人: MORTIMER M ELKIND
• 金额: $ 57.53万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3479697
• 关键词: DNA repair; DNA replication; athymic mouse; autosome; bromodeoxyuridine; carbopolycyclic compound; cell death; chemical addition; chemical carcinogenesis; cytogenetics; genetic markers; human tissue; ionizing radiation; mutagens; photobiology; psoralens; radiation carcinogenesis; radiation dosage; radiation genetics; radiation recovery; radiobiology; radiosensitizer; sex chromosomes; solar radiation; tissue /cell culture; tumor promoters; ultraviolet radiation

Radiation, and DNA-active chemicals, are generally cytotoxic, mutagenic, and oncogenic. Cell killing, which is essential in the therapy of cancer, is also important to the assessment of mutation and neoplastic transformation because cellular viability is required for both of these end effects to be expressed. Radiation is recognized as mutagenic and oncogenic in people and a number of the chemicals which are used in cancer therapy have similar properties. It follows, therefore, that the study of the biological effects of radiation and genotoxic chemicals is important both to issues of public health and to the treatment of cancer. This research will focus mainly on ionizing radiation although near-ultraviolet, sunlight-simulating light and certain chemicals will also be studied. A primary theme will be damage and repair processes in mammalian cells in culture as these processes influence lethality, mutagenesis, and neoplastic transformation. The underlying notion, which has applied to the work of the Principal Investigator over the past 30 years, is that the cell and molecular biology of damage and repair are opposite sides of the same coin. That is, progress on one aspect of the problem complements the understanding of the other. A study of mechanisms of damage and repair draws together the otherwise disparate features of the radiobiology of protracted low doses, as they may constitute an environmental hazard, and the radiobiology of single-to-protracted moderate-to-high radiation doses as they may be applied in tumor therapy. In addition, as therapy becomes more effective and lifespans are extended, the likelihood must be faced that second tumors may become expressed. An understanding of the mechanism of tumorigenesis could lead to the development of treatment strategies which minimize such risks. Thus, from another vantage point, this possibility also illustrates an essential coherence of the several parts of the proposed research.

辐射和DNA活性化学物质通常具有细胞毒性， 具有致突变性和致癌性。细胞杀灭，这在 癌症治疗，也是重要的评估 突变和肿瘤转化因为细胞的生存能力 是表达这两种最终效果所必需的。 辐射在人类中被认为是诱变和致癌的， 许多用于癌症治疗的化学物质有 相似的属性。因此，由此得出结论，对 辐射和遗传毒性化学物质的生物效应是 对公共卫生问题和治疗都很重要 癌症。 这项研究将主要集中在电离辐射上，尽管 近紫外线、模拟阳光的光线和某些化学物质 也将进行研究。一个主要主题将是损坏和修复 哺乳动物细胞在培养过程中的这些过程 影响致命性、诱变性和肿瘤转化。 基本的概念，这已经应用于 在过去的30年里，首席调查员是细胞和 损伤和修复的分子生物学是分子生物学的对立面 同样的硬币。也就是说，在问题的一个方面取得了进展 补充了对方的理解。 对损伤和修复机制的研究总结了 迁延性低的放射生物学的其他不同特征 剂量，因为它们可能构成环境危害，以及 单次至长时间中高辐射的放射生物学 在肿瘤治疗中可能应用的剂量。此外，AS 治疗变得更有效，寿命延长， 必须正视第二种肿瘤可能成为 表达。对肿瘤发生机制的认识 可能导致治疗策略的发展， 将此类风险降至最低。因此，从另一个角度来看，这 可能性也说明了以下几个方面的基本一致性 拟议研究的部分内容。