Fong L Y, Magee P N
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cancer Lett. 1999 Aug 23;143(1):63-9. doi: 10.1016/s0304-3835(99)00191-3.
The effect of zinc deficiency on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor formation in rats has been well documented. Our previous work showed that zinc deficiency and its associated increased esophageal cell proliferation were of paramount importance in esophageal tumor development in the NMBA-rat model. However, there has been no report concerning zinc deficiency and NMBA-induced esophageal tumor formation in mice. In this study, weanling C57BL/6 mice were fed ad libitum with either a zinc-sufficient or a zinc-deficient diet containing 3-4 ppm of zinc, and received six intragastric doses of NMBA (2 mg/kg; twice weekly for 3 weeks). The animals were sacrificed 46 weeks later after in vivo bromodeoxyuridine (BrDU) labeling followed by immunohistochemical detection of cells in S-phase. At 46 weeks, the tumor incidences in zinc-deficient mice were 57, 100, and 100% respectively, in the esophagus, forestomach and squamocolumnar junction with the glandular stomach (SCJ), as compared to 17, 39, and 67% in the corresponding tissue of zinc-sufficient mice. The difference between the two dietary groups was significant at P < 0.02 for the esophagus, and P < 0.001 for the forestomach and the SCJ. BrDU labeling revealed that the esophageal labeling index and the number of labeled cells were increased by zinc deficiency. These results support a role of increased cell proliferation in esophageal carcinogenesis in the mouse.
锌缺乏对N-亚硝基甲基苄胺（NMBA）诱导的大鼠食管肿瘤形成的影响已有充分记录。我们之前的研究表明，在NMBA-大鼠模型中，锌缺乏及其相关的食管细胞增殖增加在食管肿瘤发展中至关重要。然而，尚无关于锌缺乏与NMBA诱导的小鼠食管肿瘤形成的报道。在本研究中，给断乳的C57BL/6小鼠随意喂食含锌量为3 - 4 ppm的锌充足或锌缺乏饮食，并给予六次胃内注射NMBA（2 mg/kg；每周两次，共3周）。在进行体内溴脱氧尿苷（BrDU）标记后，通过免疫组织化学检测S期细胞，46周后处死动物。46周时，锌缺乏小鼠食管、前胃和胃腺部鳞状柱状交界处（SCJ）的肿瘤发生率分别为57%、100%和100%，而锌充足小鼠相应组织的肿瘤发生率分别为17%、39%和67%。两组饮食组之间，食管的差异在P < 0.02时具有统计学意义，前胃和SCJ在P < 0.001时具有统计学意义。BrDU标记显示，锌缺乏会增加食管标记指数和标记细胞数量。这些结果支持细胞增殖增加在小鼠食管癌变中起作用。
