Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Carcinogenesis. 2011 Mar;32(3):351-8. doi: 10.1093/carcin/bgq251. Epub 2010 Nov 19.
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.
锌缺乏与人类食管和其他癌症的高发有关，并导致实验鼠上消化道高度增生。补锌可降低缺锌大鼠和小鼠舌、食管和前胃肿瘤的发生率。虽然以前的动物研究集中在缺锌上，但我们已经研究了补锌对野生型和肿瘤抑制基因缺失小鼠品系中肿瘤发生的影响。所有小鼠均接受 N-亚硝基甲基苄胺处理，然后一半小鼠接受补锌。在处死时，未补锌的小鼠比补锌的小鼠发展出更多的肿瘤：野生型 C57BL/6 小鼠分别发展出 7.0 个和 5.0 个肿瘤（补锌组 P<0.05）；补锌的 Fhit-/-小鼠分别发展出 5.7 个和 8.0 个肿瘤（对照组 P<0.01）；补锌的 Fhit-/-Nit1-/-小鼠分别发展出 5.4 个和 9.2 个肿瘤（对照组 P<0.01）；补锌的 Fhit-/-Rassf1a-/-（鼠基因）小鼠分别发展出 5.9 个和 9.1 个肿瘤（对照组 P<0.01）。补锌可使肿瘤负担降低 28%（野生型）至 42%（Fhit-/-Nit1-/-）。对胃组织的组织学分析也表明，补锌组的每只小鼠品系的癌前病变和肿瘤的严重程度均显著降低。因此，补锌可显著降低多重肿瘤抑制基因缺失小鼠的肿瘤负担。当在最后一次致癌物剂量后 7 周开始补锌时，肿瘤负担的减少与在致癌物给药后立即开始补锌时观察到的减少相同，这表明补锌可能影响肿瘤进展而不是肿瘤起始。
