Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio)
Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio)
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DOI：
10.1038/labinvest.3780042
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发表时间：
2000-03-01
影响因子：
5
通讯作者：
Cheng, KC
中科院分区：
文献类型：
--
作者：
Beckwith, LG;Moore, JL;Cheng, KC
斑马鱼（Danio rerio）已被成功用于发现数百个与发育和器官发生有关的基因。为了发挥斑马鱼作为癌症模型的潜力，确定斑马鱼对肿瘤的易感性非常重要。斑马鱼突变体筛选中最常见的种系突变是通过将成年雄性斑马鱼暴露于烷化剂乙基亚硝基脲 (ENU) 中诱导的。为了确定 ENU 是否会诱发肿瘤，我们将 ENU 处理的鱼与未处理的对照鱼的肿瘤发生率进行了比较。有趣的是，用 2.5 或 3.0 mM ENU 诱变的 18 条鱼中，有 18 条（100%）在治疗一年内出现了表皮乳头状瘤，每条鱼的数量为 1 至 22 个。诱发的表皮病变包括表皮增生、扁平乳头状瘤（0.2至1.2毫米）和带蒂乳头状瘤（最大尺寸1.2至8毫米），但没有皮肤癌。大于约 1 毫米的乳头状瘤中血管生成明显。除两个乳头状瘤外，所有乳头状瘤均含有正常斑马鱼表皮的三种细胞类型（角质形成细胞、棒状细胞和粘液细胞）；组织学变异缺乏俱乐部细胞或粘液细胞。在接受治疗的鱼中还发现了两个海绵状血管瘤和一个恶性周围神经鞘瘤。五个未经治疗的对照组均未出现肿瘤。这些研究确立了斑马鱼作为皮肤肿瘤研究实验模型的可行性。
The zebrafish (Danio rerio) has been successfully used to discover hundreds of genes involved in development and organogenesis. To address the potential of zebrafish as a cancer model, it is important to determine the susceptibility of zebrafish to tumors. Germ line mutations are most commonly induced for zebrafish mutant screens by exposing adult male zebrafish to the alkylating agent, ethylnitrosourea (ENU). To determine whether ENU induces tumors, we compared the incidence of tumors in ENU-treated fish with untreated controls. Interestingly, 18 of 18 (100%) fish mutagenized with either 2.5 or 3.0 mM ENU developed epidermal papillomas, which numbered 1 to 22 per fish, within 1 year of treatment. The induced epidermal lesions included epidermal hyperplasia, flat papillomas (0.2 to 1.2 mm), and pedunculated papillomas (1.2 to 8 mm in greatest dimension), but no skin cancers. Angiogenesis was evident in papillomas larger than approximately 1 mm. All but two papillomas contained the three cell types (keratinocytes, club, and mucous cells) of normal zebrafish epidermis; histologic variants lacked either club cells or mucous cells. Two cavernous hemangiomas and a single malignant peripheral nerve sheath tumor were also found in the treated fish. None of five untreated controls developed tumors. These studies establish the feasibility of the zebrafish as an experimental model for the study of skin tumors.