RESISTANCE TO CHEMICALLY INDUCED LYMPHOMA

人们对人类基因所知甚少，这些基因可以增加 对环境致癌物的敏感性或抗药性。最激动人心 知识是从基于更广泛的 在实验动物身上获得的实验数据。这项研究建议 这里旨在阐明显著差异的遗传基础 在某些近交系小鼠中T细胞淋巴瘤的发病率 在经皮应用3-甲基胆蒽(MA)后。这个 主要目标是建立在我们之前的数据基础上，表明单个 显性基因是相对抗性的主要决定因素 淋巴增生症，并对该基因进行定位。目标将在一年内首先研究 一组新的重组近交系小鼠的DNA分析， SWXD1，通过寻找MA淋巴瘤发病率和 其他遗传多态，主要是限制性片段长度 利用内源性小鼠白血病基因探针检测基因多态性 病毒，广泛分布在小鼠的染色体中。 同样，同样的方法也将应用于DNA的分析 大回交群体中的单个小鼠为 MA耐药基因的存在或缺失与淋巴瘤的观察 经MA治疗后。另一个目标来自于实验表明 这个相同的耐药基因可能在抵抗淋巴肿大方面发挥作用。 通过分次全身照射；这种可能性还将 在SWXD 1菌株中进行研究，通过比较 每株菌株经MCA处理后与照射后的对照。第三个目标 涉及到对标记的遗传基础的探索，从基因上 Rf/J株小鼠对淋巴肿大的隐性超敏反应 低总剂量(200rad)的分割照射，与 其他在较高剂量下高度敏感但在 低剂量。我们将寻求任何关于生物机制的建议 可能是导致淋巴瘤耐药性差异的原因之一 试图将它们与抗药性的分布相关联 基因。

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.