Oka M, Furihata C, Kitoh K, Yamamoto M, Tatematsu M, Ichinose M, Miki K, Ito T, Sakaki Y, Reske K
Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Japan.
Cancer Res. 1998 Sep 15;58(18):4107-12.
The involvement of immune response in the resistance of chemically induced stomach cancer was studied in a resistant rat strain (Buffalo) and a sensitive rat strain (ACI). Groups of 10 male Buffalo and ACI rats, 6 weeks of age, were given drinking water with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; 100 mg/l) for 14 days. Total RNA was isolated from the stomach pyloric mucosa from five rats, and cDNA was prepared with reverse transcriptase. Tissue sections of the stomach pyloric mucosa from five rats were stained with antibodies recognizing molecules expressed by various immune cells. Reverse transcription-PCR (RT-PCR), competitive RT-PCR, and Northern blot demonstrated that the expression of MHC class II group genes [MHC class II, MHC class II-associated invariant chain (Ii), CD4 and IgM (B cell marker)], MHC class I group genes (MHC class I and CD8), B7-1 (costimulator on dendritic cells), and CD28 (receptor to B7 on T cells) in the pyloric mucosa was elevated by MNNG in both rat strains but was elevated to a 4-7-fold greater extent in Buffalo rats than in ACI rats. These genes were scarcely expressed in control rats. Histochemical antibody staining after MNNG exposure showed a greater number of cells stained with monoclonal antibody to Ii, OX-62 (dendritic cell marker), and ED-1 (dendritic cell and macrophage common marker) in the interstitial tissue of the pyloric mucosa of Buffalo rats compared with ACI rats. Cell proliferation, as measured by 5-bromo-2-deoxyuridine (BrdUrd)-labeling indices, revealed the presence of BrdUrd-labeled cells only among epithelial cells in the proliferative zone; cells in the interstitial tissue were not labeled with BrdUrd. The results suggest the involvement of dendritic cell response in the resistance to the MNNG induction of stomach carcinogenesis in rats.
在一种抗性大鼠品系（布法罗大鼠）和一种敏感大鼠品系（ACI大鼠）中研究了免疫反应在化学诱导的胃癌抗性中的作用。将10只6周龄的雄性布法罗大鼠和ACI大鼠分为两组，分别给予含或不含N-甲基-N'-硝基-N-亚硝基胍（MNNG；100 mg/l）的饮用水，持续14天。从5只大鼠的胃幽门黏膜中分离总RNA，并用逆转录酶制备cDNA。用识别各种免疫细胞表达分子的抗体对5只大鼠的胃幽门黏膜组织切片进行染色。逆转录-聚合酶链反应（RT-PCR）、竞争性RT-PCR和Northern印迹分析表明，两种大鼠品系中，MNNG均可使幽门黏膜中主要组织相容性复合体（MHC）Ⅱ类基因（MHCⅡ、MHCⅡ相关恒定链（Ii）、CD4和IgM（B细胞标志物））、MHCⅠ类基因（MHCⅠ和CD8）、B7-1（树突状细胞上的共刺激分子）和CD28（T细胞上B7的受体）的表达升高，但布法罗大鼠中这些基因的表达升高幅度比ACI大鼠高4至7倍。这些基因在对照大鼠中几乎不表达。MNNG暴露后的组织化学抗体染色显示，与ACI大鼠相比，布法罗大鼠幽门黏膜间质组织中用抗Ii单克隆抗体、OX-62（树突状细胞标志物）和ED-1（树突状细胞和巨噬细胞共同标志物）染色的细胞数量更多。通过5-溴-2'-脱氧尿苷（BrdUrd）标记指数测量的细胞增殖显示，仅在增殖区的上皮细胞中存在BrdUrd标记的细胞；间质组织中的细胞未被BrdUrd标记。结果表明树突状细胞反应参与了大鼠对MNNG诱导胃癌的抗性。
