Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach tumor development and progression in tumor suppressor-deficient mouse strains.
Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach tumor development and progression in tumor suppressor-deficient mouse strains.
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DOI：
10.1093/carcin/bgq251
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发表时间：
2011-03
期刊：
影响因子：
4.7
通讯作者：
J. Sun;James Liu;X. Pan;Donald Quimby;N. Zanesi;T. Druck;G. Pfeifer;C. Croce;L. Fong;
中科院分区：
文献类型：
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作者：
J. Sun;James Liu;X. Pan;Donald Quimby;N. Zanesi;T. Druck;G. Pfeifer;C. Croce;L. Fong;
锌缺乏与人类食管癌和其他癌症的高发病率相关，并导致实验室啮齿动物上胃肠道高度增殖性增生。补充锌可降低锌缺乏大鼠和小鼠的舌、食管和前胃肿瘤的发生率。虽然以前的动物研究集中在锌缺乏症，我们已经调查了锌补充剂对锌充足的野生型和肿瘤抑制基因缺陷小鼠品系的致癌作用。所有小鼠均接受N-亚硝基甲基苄胺，然后每种品系的一半小鼠接受锌补充剂。在处死时，没有补充锌的小鼠比补充锌的小鼠发展了更多的肿瘤：野生型C57 BL/6小鼠平均发展了7.0个肿瘤，而补充锌的小鼠平均发展了5.0个肿瘤。（P < 0.05）;补充Zn的Fhit-/-小鼠的平均值为5.7，而对照小鼠为8.0（P < 0.01）;补充Zn的Fhit-/-Nit 1-/-小鼠平均为5.4对对照小鼠的9.2（P < 0.01），补充Zn的Fhit-/-Rassf 1a-/-（鼠基因）小鼠平均为5.9对对照小鼠的9.1（P < 0.01）。补充锌可使肿瘤负荷降低28%（野生型）至42%（Fhit-/-Nit 1-/-）。前胃组织的组织学分析还显示，在每个小鼠品系的锌补充队列中，癌前病变和肿瘤病变的严重程度显著降低。因此，锌补充剂显着降低肿瘤负荷的小鼠与多种肿瘤抑制基因缺陷。当在最终致癌物给药后7周开始补充锌时，肿瘤负荷的减少与在致癌物给药后立即开始补充时观察到的相同，这表明锌补充可能影响肿瘤进展而不是肿瘤起始。
Zinc deficiency is associated with high incidences of esophageal and other cancers in humans and leads to a highly proliferative hyperplastic condition in the upper gastrointestinal tract in laboratory rodents. Zn replenishment reduces the incidence of lingual, esophageal and forestomach tumors in Zn-deficient rats and mice. While previous animal studies focused on Zn deficiency, we have investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice of wild-type and tumor suppressor-deficient mouse strains. All mice received N-nitrosomethylbenzylamine and half the mice of each strain then received Zn supplementation. At killing, mice without Zn supplementation had developed more tumors than Zn-supplemented mice: wild-type C57BL/6 mice developed an average of 7.0 versus 5.0 tumors for Zn supplemented (P < 0.05); Zn-supplemented Fhit-/- mice averaged 5.7 versus 8.0 for control mice (P < 0.01); Zn-supplemented Fhit-/-Nit1-/- mice averaged 5.4 versus 9.2 for control mice (P < 0.01) and Zn-supplemented Fhit-/-Rassf1a-/- (the murine gene) mice averaged 5.9 versus 9.1 for control mice (P < 0.01). Zn supplementation reduced tumor burdens by 28% (wild-type) to 42% (Fhit-/-Nit1-/-). Histological analysis of forestomach tissues also showed significant decreases in severity of preneoplastic and neoplastic lesions in Zn-supplemented cohorts of each mouse strain. Thus, Zn supplementation significantly reduced tumor burdens in mice with multiple tumor suppressor deficiencies. When Zn supplementation was begun at 7 weeks after the final carcinogen dose, the reduction in tumor burden was the same as observed when supplementation began immediately after carcinogen dosing, suggesting that Zn supplementation may affect tumor progression rather than tumor initiation.