RESISTANCE TO CHEMICALLY INDUCED LYMPHOMA

对化学诱发淋巴瘤的抵抗力

• 批准号: 2094860
• 负责人: FRANK LILLY
• 金额: $ 26.75万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2094860
• 关键词: DNA; autosomal dominant trait; chemical carcinogen; chemical carcinogenesis; endonuclease; environment related neoplasm /cancer; genetic markers; genetic strain; laboratory mouse; linkage mapping; lymphoma; methylcholanthrene; nucleic acid probes

Very little is known about human genes that can confer increased susceptibility or resistance to environmental carcinogens. Most exciting knowledge has been obtained from studies based on the much extensive experimental data obtained in laboratory animals. The studies proposed here are aimed at elucidating the genetic basis of the marked differences in the incidence of T-cell lymphoma among mice of certain inbred strains following percutaneous application of 3-methylcholanthrene (MA). The primary goal is to build upon our previous data indicating that a single dominant gene is the major determinant of relative resistance to MA lymphomagenesis and to map this gene. The goal will be studied first in an analysis of DNA from mice of a new set of recombinant inbred (RI) mice, SWXD1, by searching for correlations between MA lymphoma incidence and other genetic polymorphisms, primarily restriction fragment length polymorphisms detected by the use of probes for endogenous murine leukemia viruses, that are widely distributed among the chromosomes of mice. Similarly, this same approach will be applied to the analysis of DNAs from individual mice of a large backcross population segregating for the presence or absence of the MA resistance gene and observed for lymphoma after MA treatment. Another goal stems from experiments suggesting that this same resistance gene may play a role in resistance to lymphomagenesis by fractionated doses of whole body irradiation; this possibility will also be studied in the SWXD1 strains by comparing the lymphoma incidences in each strain after treatment with MCA vs. irradiation. A third goal involves the exploration of the genetic basis for the marked, genetically recessive hypersensitivity of mice of the RF/J strain to lymphomagenesis by a low total dose (200 rad) of fractionated irradiation, by comparison with other strains that are highly susceptible at higher doses but resistant at the low dose. We will pursue any suggestions of biological mechanisms that might be responsible for these differences in lymphoma resistance by attempting to correlate them with the distributions of the resistance genes.

关于可以增加增加的人类基因知之甚少 对环境致癌物的敏感性或抗性。 最令人兴奋 基于广泛的研究，已经从研究中获得了知识 实验动物获得的实验数据。 研究提出 这里旨在阐明明显差异的遗传基础 在某些近交菌株的小鼠中T细胞淋巴瘤的发生率 经经皮施用3-甲基胆碱（MA）。 这 主要目标是建立我们以前的数据，表明一个 主要基因是对MA相对抗性的主要决定因素 淋巴作用并绘制该基因。 目标将首先研究 一组新的重组近交（RI）小鼠的小鼠的DNA分析， SWXD1，通过寻找MA淋巴瘤发生率与 其他遗传多态性，主要是限制片段长度 通过使用探针进行内源性鼠白血病检测到的多态性 病毒广泛分布在小鼠的染色体之间。 同样，这种方法将应用于对DNA的分析 大型反向交叉种群的单个小鼠隔离 MA耐药基因的存在或不存在，并观察到淋巴瘤 MA治疗后。 另一个目标源于实验，表明 相同的抗性基因可能在抗淋巴作用的抗性中发挥作用 通过全身照射的分离剂量；这种可能性也将 通过比较中的SWXD1菌株研究 用MCA与辐射治疗后的每种菌株。 第三个目标 涉及对标记的，遗传学上的遗传基础的探索 RF/J菌株小鼠对淋巴作用的遗传性超敏反应 相比之下 其他高剂量高度敏感但在 低剂量。 我们将寻求任何生物学机制的建议 可能导致了这些因淋巴瘤抗性的差异的原因 试图将它们与电阻的分布相关联 基因。