5-aza-2′-deoxycytidine is chemopreventive in a 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone-induced primary mouse lung tumor model
5-aza-2′-deoxycytidine is chemopreventive in a 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone-induced primary mouse lung tumor model
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DOI：
10.1093/carcin/20.2.343
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发表时间：
1999-02-01
期刊：
影响因子：
4.7
通讯作者：
You, M
中科院分区：
文献类型：
--
作者：
Lantry, LE;Zhang, ZQ;You, M
癌变是一个多步骤的过程，其中遗传和表观遗传控制的许多改变导致肿瘤细胞的生长优势。超甲基化已被确立为基因组印迹的基础，但最近的研究也表明，基因组甲基化模式的改变可能有助于肿瘤的发生。化学物质5-氮杂-2 '-脱氧胞苷5-aza-dC在体内外均被用于抑制DNA甲基化。在本研究中，我们研究了5-aza-dC在良好建立的原发性小鼠肺肿瘤模型中的化学预防功效，（C3 H/HeJ x A/J）F-1杂交小鼠用5-aza-dC连续处理24周，每周三次i. p.用连续两周剂量的4-（甲基-亚硝氨基）-1-在用5-氮杂-dC初始处理后1周开始，我们证明了5-氮杂-dC在该原发性小鼠肺肿瘤模型中表现出化学预防作用，如人肺腺癌，具有激活性K-rns突变。用5-aza-dC治疗导致肿瘤发生率降低23%，以及肿瘤多样性降低42%。这项工作支持进一步研究甲基化抑制剂如5-aza-dC用于肺癌的早期干预，预防和治疗。
Carcinogenesis is a multistep process in which many alterations in both genetic and epigenetic controls lead to a growth advantage for neoplastic cells. Hypermethylation has been established as the basis of genomic imprinting, but recent studies have also shown that alterations in genomic methylation patterns may contribute to tumorigenesis. The chemical 5-aza-2'-deoxycytidine (5-aza-dC) has been used both in vitro and in vivo to inhibit DNA methylation, In this study, we investigated the chemopreventive efficacy of 5-aza-dC in a well-established primary mouse lung tumor model, Five-week-old male (C3H/HeJ x A/J) F-1 hybrid mice were treated for 24 consecutive weeks with 5-aza-dC, three times per week i.p. Lung tumors were induced with two consecutive weekly doses of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone starting 1 week after initial treatment with 5-aza-dC, We demonstrated that 5-aza-dC exhibits a chemopreventive effect in this primary mouse lung tumor model which, like human lung adenocarcinomas, harbors an activating K-rns mutation. Treatment with 5-aza-dC resulted in a 23% reduction in tumor incidence, as well as a 42% reduction in tumor multiplicity. This work supports further investigation of methylation inhibitors likes 5-aza-dC for early intervention, prevention and treatment of lung cancer.