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Carcinogenesis Experiments Using Human Skin Xenografted onto SCID-lineage Mice

使用人类皮肤异种移植到 SCID 谱系小鼠的致癌实验

基本信息

批准号：
07670937
负责人：
SAIDA Toshiaki
金额：
$ 1.22万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670937/
关键词：
CARCINOGENESIS HUMANSKIN IN VIVO EXPERIMENT SCID MOUSE XENOGRAFT PRECANCEROUS LESIONS in vivo 実験系

项目摘要

Carcinogenesis experiments have been performed in in vivo study system of mouse skin that is applied with chemical carcinogens or in vitro study system using cultured cells. Although these experiments have recently revealed a lot of information on carcinogenesis at molecular levels, precise carcinogenesis process in human organs is still unclear. Of course, it is not permitted to perform in vivo carcinogenesis experiments in humans. To produce a new in vivo experimental system of human skin, we tried to use human normal or diseasedskin transplanted onto scid-lineage mice and performed carcinogenesis experiments using the system. The following results were obtained by the present study.1. It was revealed that nude-scidmice is an excellent recipient of human skin graft. Grafted human skin on this mouse was well maintained and could be used for various kinds of experiments.2. Atypical cells of human precancerous skin lesions such as Bowen's disease survived in the grafts transplanted onto nude-scidor beige-scid mice. The survival rate in nude-scidmice was better than that in beige-scidmice. Progression into invasive carcinoma was hardly observed, however, a lesion of Bowen's disease transplanted onto a beige-scid mouse showed progression into invasive SCC during 223 days' observation period.3. Application of a chemical carcinogen, DMBA,to transplanted human skin accompanied with UVB irradiation did not produce obvious cancer macroscopically. Microscopic examination, however, revealed that intraepidemal proliferation of atypical keratinocytes in some of the skin grafts.

致癌实验已在使用化学致癌剂的小鼠皮肤体内研究系统或使用培养细胞的体外研究系统中进行。尽管这些实验最近在分子水平上揭示了很多关于癌变的信息，但人体器官的精确癌变过程仍不清楚。当然，在人体上进行体内致癌实验是不允许的。为了建立一种新的人体皮肤体内实验系统，我们尝试将人类正常或患病的皮肤移植到scid系小鼠身上，并利用该系统进行致癌实验。本研究得到以下结果： 1．研究表明，裸鼠是人类皮肤移植的良好接受者。该小鼠移植的人皮保存完好，可用于各种实验。 2．人类癌前皮肤病变（例如鲍文氏病）的非典型细胞在移植到裸-scidor米色-scid小鼠身上的移植物中存活下来。裸鼠的存活率优于米色鼠。几乎没有观察到进展为浸润性癌，然而，移植到米色-scid小鼠上的Bowen病灶在223天的观察期内显示进展为浸润性鳞状细胞癌。3．将化学致癌剂DMBA应用于人体移植皮肤并同时进行UVB照射，宏观上并未产生明显的癌症。然而，显微镜检查显示，在一些皮肤移植物中，非典型角质形成细胞在表皮内增殖。