Lu L M, Shisa H, Tanuma J, Hiai H
Department of Pathology and Biology of Disease, Graduate School of Medicine, Kyoto University, Japan.
Br J Cancer. 1999 May;80(5-6):855-61. doi: 10.1038/sj.bjc.6690432.
Oral administration of propylnitrosourea (PNU) in drinking water induces high incidence of lympho-haemopoietic malignancies in rats. Previously we reported that F344 strain rats were highly susceptible to T-lymphomas, and LE/Stm rats, to erythro- or myeloid leukaemias. For analysis of the genetic factors determining types of diseases, we have established LEXF recombinant inbred strains of rats comprising 23 substrains, each derived from intercross between F344 and LE/Stm rats. Rats of 23 LEXF substrains were given PNU, and the development of tumours was observed. The overall incidence of haemopoietic tumours ranged from 100% to 66.7%, and the fractions of T-lymphomas, from 100% to 4%, showing a continuous spectrum. Based on the genetic profile published as a strain distribution pattern table for the LEXF, we screened the potential quantitative trait loci involved in determination of the types of disease and length of the latency period. Statistical calculation was performed using the Map Manager QT software developed by Manly. Four loci, on chromosome 4, 7, 10 and 18, were suggested to associate with the T-lymphoma susceptibility and three loci, on chromosome 1, 5 and 16, with the length of the latency period. These putative loci were further examined in backcross (F344 x LE)F1 x LE. Among seven loci suggested by the recombinant inbred study, three loci, on chromosome 5, 7 and 10, were significantly associated with T-lymphomas and another locus on chromosome 1, just weakly. These observations indicate that PNU-induced lymphomagenesis is a multifactorial genetic process involving a number of loci linked with susceptibility and resistance.
在饮用水中口服丙基亚硝基脲（PNU）可在大鼠中诱发高发性淋巴造血系统恶性肿瘤。此前我们报道，F344品系大鼠对T淋巴瘤高度易感，而LE/Stm大鼠则对红白血病或髓性白血病易感。为分析决定疾病类型的遗传因素，我们建立了由23个亚系组成的LEXF重组近交系大鼠，每个亚系均源自F344和LE/Stm大鼠的杂交。给23个LEXF亚系的大鼠投喂PNU，并观察肿瘤的发生情况。造血肿瘤的总体发生率在100%至66.7%之间，T淋巴瘤的比例在100%至4%之间，呈现出连续的谱系。根据作为LEXF品系分布模式表发表的遗传图谱，我们筛选了与疾病类型和潜伏期长短决定相关的潜在数量性状位点。使用Manly开发的Map Manager QT软件进行统计计算。结果表明，位于4号、7号、10号和18号染色体上的四个位点与T淋巴瘤易感性相关，位于1号、5号和16号染色体上的三个位点与潜伏期长短相关。在回交（F344×LE）F1×LE中对这些推定的位点进行了进一步研究。在重组近交研究提示的七个位点中，位于5号、7号和10号染色体上的三个位点与T淋巴瘤显著相关，位于1号染色体上的另一个位点相关性较弱。这些观察结果表明，PNU诱导的淋巴瘤发生是一个多因素遗传过程，涉及许多与易感性和抗性相关的位点。
