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紫外线诱导黑色素瘤的动物模型:剑尾鱼-新月鱼杂交种。

Animal model for ultraviolet radiation-induced melanoma: platyfish-swordtail hybrid.

作者信息

Setlow R B, Woodhead A D, Grist E

机构信息

Biology Department, Brookhaven National Laboratory, Upton, NY 11973.

出版信息

Proc Natl Acad Sci U S A. 1989 Nov;86(22):8922-6. doi: 10.1073/pnas.86.22.8922.

Abstract

Sunlight exposure is strongly indicated as one of the important etiologic agents in human cutaneous malignant melanoma. However, because of the absence of good animal models, it has not been possible to estimate the wavelengths or wavelength regions involved. We have developed a useful animal model from crosses and backcrosses of platyfish (Xiphophorus maculatus) and swordtails (Xiphophorus helleri). Two strains of these fish are susceptible to invasive melanoma induction by exposure to filtered radiation from sunlamps in the wavelength ranges lambda greater than 290 nm and lambda greater than 304 nm. Multiple exposures on 5-20 consecutive days beginning on day 5 after birth or a single exposure of approximately 200 J/(m2.day) of lambda greater than 304 nm result in a tumor prevalence of 20% to 40% at 4 months of age compared with a background rate of 12% in one strain and 2% in another. Exposure of the fish to visible light after UV exposure reduces the prevalence to background. The melanomas are similar in many respects to mammalian melanomas, as judged by light and electron microscopy. The genetics of the crosses determined by others and the high sensitivity of the hybrids to melanoma induction indicate that the UV radiation probably inactivates the one tumor repressor gene (or a small number of tumor repressor genes) in the hybrid fish. The small size of the animals and their high susceptibility to melanoma induction make them ideal for action spectroscopy.

摘要

阳光照射被强烈认为是人类皮肤恶性黑色素瘤的重要病因之一。然而,由于缺乏良好的动物模型,一直无法估计所涉及的波长或波长范围。我们通过剑尾鱼(Xiphophorus helleri)和新月鱼(Xiphophorus maculatus)的杂交和回交培育出了一种有用的动物模型。这两种鱼的两个品系在暴露于波长范围λ大于290nm和λ大于304nm的太阳灯过滤辐射后易诱发侵袭性黑色素瘤。出生后第5天开始连续5 - 20天的多次照射,或单次暴露于约200 J/(m2·天)的λ大于304nm的辐射下,在4个月龄时肿瘤发生率为20%至40%,而其中一个品系的背景发生率为12%,另一个品系为2%。紫外线照射后再让鱼暴露于可见光下,肿瘤发生率会降至背景水平。通过光学显微镜和电子显微镜判断,这些黑色素瘤在许多方面与哺乳动物黑色素瘤相似。其他人确定的杂交遗传学以及杂种对黑色素瘤诱导的高敏感性表明,紫外线辐射可能使杂种鱼中的一个肿瘤抑制基因(或少数肿瘤抑制基因)失活。这些动物体型小且对黑色素瘤诱导高度敏感,使其成为作用光谱学的理想研究对象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8067/298402/a4534cdfdd8a/pnas00289-0338-a.jpg

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