Melhem M F, Kunz H W, Gill T J
Department of Pathology, University of Pittsburgh School of Medicine, PA 15261.
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1967-71. doi: 10.1073/pnas.90.5.1967.
Major histocompatibility complex (MHC)-linked deletions in the rat are associated with defects in growth and development and increased susceptibility to chemical carcinogens. The present study maps a locus critical for determining susceptibility to diethylnitrosamine (DEN) carcinogenesis by using two groups of MHC-recombinant rats congenic for the MHC and its linked region. Resistance to DEN segregates with a locus (rcc+) that maps between RT1.E and ft, and its homozygous loss markedly increases susceptibility to DEN. Non-MHC genes do not significantly influence the susceptibility of these strains to DEN. The existence of the rcc locus adds support to our hypothesis that some genes in the MHC-linked region play a major role in both normal and abnormal growth.
大鼠体内主要组织相容性复合体(MHC)相关的缺失与生长发育缺陷以及对化学致癌物易感性增加有关。本研究通过使用两组在MHC及其连锁区域同基因的MHC重组大鼠,定位了一个对决定二乙基亚硝胺(DEN)致癌易感性至关重要的基因座。对DEN的抗性与一个位于RT1.E和ft之间的基因座(rcc+)共分离,该基因座的纯合缺失显著增加了对DEN的易感性。非MHC基因对这些品系对DEN的易感性没有显著影响。rcc基因座的存在支持了我们的假设,即MHC连锁区域中的一些基因在正常和异常生长中都起主要作用。