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利用 Xiphophorus 黑色素瘤模型研究阳光诱导致癌作用的最新进展。

Recent advances in sunlight-induced carcinogenesis using the Xiphophorus melanoma model.

机构信息

The University of Texas MD Anderson Cancer Center, Department of Carcinogenesis, 1808 Park Road 1C, Smithville, TX 78957, USA.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2012 Jan;155(1):64-70. doi: 10.1016/j.cbpc.2011.03.007. Epub 2011 Mar 30.

Abstract

Unlike breast and prostate cancers, the nature and sequence of critical genetic and epigenetic events involved in the initiation and progression of melanoma are not well understood. A contributing factor to this dilemma, especially given our current understanding of the importance of UV light in melanoma etiology, is the lack of quality UV-inducible melanoma animal models. In this study we elaborate on the capability of UV light to induce cutaneous malignant melanomas (CMM) in Xiphophorus fishes, which were previously found to develop melanomas after acute neonatal UVB irradiation. In two separate tumorigenesis experiments, we exposed adult Xiphophorus hybrids to either acute UVB irradiations (5 consecutive daily treatments) or chronic solar irradiations (continuous UVA/UVB treatment for 9 months). Acute adult UVB irradiation resulted in the significant induction of melanomas, and moreover, this induction rate is equivalent to that of animals exposed to acute neonatal UVB irradiation. This study represents the first evidence that acute adult UVB irradiation, in the absence of any early life exposures, induces CMM. Similar to the findings conducted on other divergent melanoma models, including HGF/SF transgenic mice and Monodelphis domestica, prolonged chronic solar UV was not a factor in melanomagenesis.

摘要

与乳腺癌和前列腺癌不同,黑色素瘤起始和进展中涉及的关键遗传和表观遗传事件的性质和顺序还没有被很好地理解。造成这种困境的一个因素,特别是考虑到我们目前对紫外线在黑色素瘤病因学中的重要性的理解,是缺乏高质量的紫外线诱导黑色素瘤动物模型。在这项研究中,我们详细阐述了紫外线诱导 Xiphophorus 鱼类皮肤恶性黑色素瘤(CMM)的能力,先前的研究发现,Xiphophorus 鱼类在急性新生儿 UVB 照射后会发展出黑色素瘤。在两个独立的肿瘤发生实验中,我们分别将成年 Xiphophorus 杂交种暴露于急性 UVB 照射(连续 5 天治疗)或慢性太阳照射(连续 UVA/UVB 治疗 9 个月)。急性成年 UVB 照射显著诱导了黑色素瘤,而且,这种诱导率与暴露于急性新生儿 UVB 照射的动物相当。这项研究首次证明,在没有任何早期生活暴露的情况下,急性成年 UVB 照射会诱导 CMM。与在其他不同的黑色素瘤模型(包括 HGF/SF 转基因小鼠和 Monodelphis domestica)上进行的研究结果相似,长期慢性太阳 UV 并不是黑色素瘤发生的因素。

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