Photocarcinogenesis and susceptibility to UV radiation in the v-Ha-ras transgenic Tg.AC mouse.

Photocarcinogenesis and susceptibility to UV radiation in the v-Ha-ras transgenic Tg.AC mouse.
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v-Ha-ras 转基因 Tg.AC 小鼠的光致癌作用和对紫外线辐射的敏感性。

DOI:
10.1046/j.1523-1747.1998.00237.x
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发表时间:
1998
期刊:
The Journal of investigative dermatology.
影响因子:
--
通讯作者:
Tennant,RW
Tennant,RW
中科院分区:
--
文献类型:
--
作者:
Trempus,CS;Mahler,JF;Ananthaswamy,HN;Loughlin,SM;French,JE;Tennant,RW

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已证明v-Ha-ratransgenic Tg.AC小鼠系是研究化学致癌潜力的有用模型。我们进行了实验,旨在研究物理致癌物质,紫外线辐射,对这种小鼠品系的肿瘤发生的影响。在总共三次暴露在交替的日子,以辐射源覆盖的累积UVR暴露范围为2.6-42.6千焦每平方米,鳞状乳头状瘤开发的4周后,首次曝光的剂量依赖性的方式。肿瘤发生在18-30周内的初始UVR曝光后,所有被诊断为鳞状细胞癌或梭形细胞肿瘤。与光致癌研究中使用的其他小鼠品系相比,在聚合酶链反应-单链构象多态性分析外显子4-8,然后对可疑条带进行测序后,在Tg.AC恶性肿瘤中发现了很少的wp 53突变;然而,通过原位杂交分析的所有肿瘤均表达v-Ha-ras转基因。免疫组织化学分析的紫外线暴露的皮肤后24小时采取的最后三个曝光(13.1千焦每平方米总紫外线)显示的毛囊和毛囊间表皮中的p53的表达,这表明该基因的功能。因此,尽管Tg.AC小鼠模型与其他小鼠模型之间存在一些差异,但这些结果表明Tg.AC小鼠可能是研究急性暴露光致癌作用的有用模型。
The v-Ha-rastransgenic Tg.AC mouse line has proven to be a useful model for the study of chemical carcinogenic potential. We undertook experiments designed to study the effect of the physical carcinogen, UV radiation, on tumorigenesis in this mouse strain. Following a total of three exposures on alternating days to a radiation source covering a cumulative UVR exposure range of 2.6–42.6 kJ per m2, squamous papillomas developed by 4 wk after initial exposure in a dose-dependent manner. Malignancies developed within 18–30 wk following the initial UVR exposure and were all diagnosed as squamous cell carcinoma or spindle cell tumors. In contrast to other mouse stains used in photocarcinogenesis studies, fewp53mutations were found in Tg.AC malignancies upon polymerase chain reaction-single stranded conformational polymorphism analysis of exons 4–8 followed by sequencing of suspicious bands; however, all tumors analyzed byin situhybridization expressed the v-Ha-rastransgene. Immunohistochemical analysis of UVR-exposed skin taken 24 h after the last of three exposures (13.1 kJ per m2total UVR) showed expression ofp53in hair follicles and in interfollicular epidermis, which indicates that the gene was functional. Thus, although there are some differences between the Tg.AC and other mouse models, these results suggest that the Tg.AC mouse may be a useful model for the study of acute exposure photocarcinogenesis.