RESISTANCE TO CHEMICALLY INDUCED LYMPHOMA IN MICE

我们对人类基因知之甚少， 对环境致癌物的敏感性或抵抗力。 最令人兴奋 知识已经从基于广泛的研究中获得， 在实验室动物中获得的实验数据。 建议的研究 本文旨在阐明这些显著差异的遗传基础。 某些近交系小鼠T细胞淋巴瘤的发病率 经皮应用3-甲基胆蒽（MA）后。 的 主要目标是建立在我们以前的数据表明，一个单一的 显性基因是决定MA相对抗性的主要基因 淋巴瘤发生和定位该基因。 该目标将首先在一个 来自一组新的重组近交系（RI）小鼠的DNA分析， SWXD 1，通过搜索MA淋巴瘤发病率与 其他遗传多态性，主要是限制性片段长度 内源性小鼠白血病探针多态性检测 病毒，广泛分布在小鼠的染色体中。 同样，这种方法也将应用于分析DNA， 分离的大回交群体的个体小鼠 存在或不存在MA耐药基因，并观察淋巴瘤 MA治疗后。 另一个目标源于实验表明， 同样的抗性基因可能在抵抗淋巴瘤发生中起作用 通过分次剂量的全身照射;这种可能性也将 在SWXD 1株中进行研究， 用MCA处理后的每种菌株与辐照。 第三个进球 涉及到对标记的遗传基础的探索， RF/J品系小鼠对淋巴瘤发生的隐性超敏反应， 低总剂量（200拉德）的分次照射，相比之下， 其他菌株在较高剂量下高度敏感， 低剂量。 我们将继续研究任何生物学机制的建议， 可能是淋巴瘤耐药性差异的原因， 试图将它们与电阻分布联系起来 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.