Talcott P A, Exon J H, Koller L D
Department of Veterinary Science, University of Idaho, Moscow 83843.
Carcinogenesis. 1990 May;11(5):829-34. doi: 10.1093/carcin/11.5.829.
Eight-week-old male Sprague-Dawley rats were exposed to the carcinogen methylnitrosourea (MNU) via gastric intubation at doses of either 10 or 20 mg/kg body wt. Rats were treated once a week for 4 weeks, then once every 2 weeks for 1 month, for a total of 6 treatments. MNU was found to exert no consistent significant immunosuppressive effects in vivo as measured by spleen natural killer (NK) cell cytotoxicity, interleukin-2 (IL-2) production by splenic lymphocytes and prostaglandin E2 (PGE2) production by adherent peritoneal macrophages. In contrast, splenic NK cell cytotoxicity and IL-2 production of MNU-treated rats were actually elevated at several of the later sampling periods. PGE2 production was also elevated in MNU-treated rats in the later sampling periods. Body weights of MNU-treated rats were markedly decreased as early as 4 weeks following the initial MNU treatment. This suppression persisted throughout the study. The most dramatic change in organ weights was seen in the thymus. Thymus weights of all MNU-treated rats were significantly decreased 1 day after treatment and persisted for 4 weeks. By the 60 day sampling period, thymus weights were not significantly different from controls. However, by 120 and 180 days, thymus weights again were significantly lowered in those rats receiving MNU. These changes in thymus weights were accompanied histologically by initial cortical thinning and progressive loss of cortical thymocytes followed by the appearance of hyperplastic and neoplastic cells. It thus appears that the carcinogenic effect of MNU is not related to a depression of the immune surveillance system, at least as measured by NK cell activity.
八周龄雄性Sprague-Dawley大鼠通过胃管给予致癌剂甲基亚硝基脲（MNU），剂量为10或20mg/kg体重。大鼠每周治疗一次，共治疗4周，然后每两周治疗一次，持续1个月，总共治疗6次。通过脾脏自然杀伤（NK）细胞细胞毒性、脾淋巴细胞产生白细胞介素-2（IL-2）以及贴壁腹膜巨噬细胞产生前列腺素E2（PGE2）来衡量，发现MNU在体内未产生一致的显著免疫抑制作用。相反，在几个后期采样期，MNU处理大鼠的脾脏NK细胞细胞毒性和IL-2产生实际上有所升高。在后期采样期，MNU处理大鼠的PGE2产生也有所升高。早在首次MNU处理后4周，MNU处理大鼠的体重就明显下降。这种抑制在整个研究过程中持续存在。器官重量变化最显著的是胸腺。所有MNU处理大鼠的胸腺重量在处理后1天显著下降，并持续4周。到60天采样期时，胸腺重量与对照组无显著差异。然而，到120天和180天时，接受MNU的大鼠胸腺重量再次显著降低。这些胸腺重量的变化在组织学上伴随着最初的皮质变薄和皮质胸腺细胞的逐渐丢失，随后出现增生性和肿瘤性细胞。因此，至少通过NK细胞活性来衡量，MNU的致癌作用似乎与免疫监视系统的抑制无关。
