Mise-Omata S, Sugiura T, Higashi K, Yamashita U
Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyusyu.
Jpn J Cancer Res. 1999 Dec;90(12):1277-84. doi: 10.1111/j.1349-7006.1999.tb00709.x.
Carcinogen-resistant DRH rats were developed from carcinogen-sensitive Donryu rats, which showed a high incidence of hepatic tumors when they were exposed to 3'-methyl-4-dimethyl-amino-azobenzene (3'-MeDAB4) or other aminoazo hepatocarcinogens. In order to study the mechanism of the difference of carcinogenesis, we studied the immunological competence of Donryu rats compared with that of DRH rats. Anti-keyhole limpet hemocyanin (KLH) antibody and KLH-specific delayed hypersensitivity (DTH) responses after immunization with KLH were reduced in Donryu rats compared with DRH rats. Proliferative responses of spleen cells to KLH and nonspecific mitogens such as conconavalin A (Con A) and phytohemagglutinin (PHA) were significantly lower in Donryu rats than in DRH rats. Upon the cross-linking of T cell receptor (TCR) complex using anti-CD3 monoclonal antibody (Mab), spleen cells from Donryu rats proliferated poorly. Two other strains of rats, SD and Wistar, exhibited high responsiveness, comparable to that of DRH rats, indicating that the responsiveness of Donryu rats was impaired. The production of interleukin-2 (IL-2) upon stimulation with Con A and the responsiveness of Con A blasts to exogenous IL-2 were also attenuated in Donryu rats. In contrast to T cell responsiveness, natural killer (NK) cell activity of spleen was increased in Donryu rats. Flow cytometric analysis revealed that the expression of CD4 and CD8 on T cells was decreased in Donryu rats, though the expression of other T cell markers such as CD2, CD3 and CD5 was not different. These results indicate that Donryu rats, which have been used in many years for cancer research in Japan, have impaired immunological surveillance mechanisms. This is likely to be one of the factors accounting for the high sensitivity to chemical carcinogens and the high susceptibility to transplanted tumor cells of Donryu rats.
抗致癌物的DRH大鼠是由对致癌物敏感的唐林大鼠培育而来，唐林大鼠在接触3'-甲基-4-二甲基氨基偶氮苯（3'-MeDAB4）或其他氨基偶氮类肝癌致癌物时，肝肿瘤发病率很高。为了研究致癌差异的机制，我们将唐林大鼠与DRH大鼠的免疫能力进行了比较研究。与DRH大鼠相比，唐林大鼠在用钥孔戚血蓝蛋白（KLH）免疫后，抗KLH抗体和KLH特异性迟发型超敏反应（DTH）降低。唐林大鼠脾细胞对KLH以及诸如刀豆球蛋白A（Con A）和植物血凝素（PHA）等非特异性有丝分裂原的增殖反应明显低于DRH大鼠。使用抗CD3单克隆抗体（Mab）交联T细胞受体（TCR）复合物后，唐林大鼠的脾细胞增殖能力较差。另外两种大鼠品系，SD和Wistar，表现出与DRH大鼠相当的高反应性，这表明唐林大鼠的反应性受损。唐林大鼠在用Con A刺激后白细胞介素-2（IL-2）的产生以及Con A母细胞对外源IL-2的反应性也减弱。与T细胞反应性相反，唐林大鼠脾的自然杀伤（NK）细胞活性增加。流式细胞术分析显示，唐林大鼠T细胞上CD4和CD8的表达降低，不过其他T细胞标志物如CD2、CD3和CD5的表达没有差异。这些结果表明，在日本多年来用于癌症研究的唐林大鼠，其免疫监视机制受损。这可能是唐林大鼠对化学致癌物高度敏感以及对移植肿瘤细胞高度易感的因素之一。
