Research if interactions between chemical carcinogens, physical irritations and papillomavirus in carcinogenesis

研究化学致癌物、物理刺激和乳头瘤病毒在致癌过程中的相互作用

• 批准号: 11671832
• 负责人: MAEDA Hatsuhiko
• 金额: $ 2.24万
• 依托单位: Aichi-Gakuin University School of Dentistry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671832/
• 关键词: hamster; animal; papillomavirus; carcinogenesis; wound healing; immunity

In a previous investigation, we developed a highly reproducible carcinogenesis model by combining DMBA application with physical wounding of the hamster lingual mucosa. Histologically, these lesions showed pathognomonic changes indicative of papillomavirus infection, such as koilocytosis of dysplastic cells, and the nuclei of some dysplastic or cancerous cells were positive for papillomavirus genus-specific antigen (GSA). Furthermore, viral particles resembling papillomavirus, whose 0size was 50-55 nm in diameter, have been detected in the nuclei of these cells.Using this animal model, we demonstrated the presence of a novel hamster papillomavirus by the molecular cloning and sequencing of this viral genome. The genome was confirmed by complete sequence analysis to be a novel papillomavirus which we designated the hamster oral papillomavirus (HOPV). Moreover, we detected HOPV in the nuclei of dysplastic and malignant lesions in hamster lingual epithelium using in situ hybridization. Computer-assisted phylogenetic analysis of HOPV showed a differing homology with other papillomaviruses in different regions of the genomes. The complete nucleotide sequence of this viral genome consists of 7647bp with a G+C content of 46.6%. This size is similar to that of MnPV (7687bp). This genome has open reading frames (ORFs) on one strand showing the usual order : ORFs E6, E7, E1, E2, L2 and L1. ORF E2 contains the small ORF E4. ORF E5 is missing. These cloned genomes are different from those of other rodent papillomaviruses, such as MmPV and MnPV, and also from previously sequenced animal and human papillomavirus genomes.Therefore, HOPV infection seems to be a good model for the study on mucosal carcinogenesis associated with papillomavirus and for studies on vaccine prophylaxis and the prevention or treatment of malignant conversion.

在之前的研究中，我们开发了一种高度重复性的致癌模型，将DMBA的应用与对金黄地鼠舌粘膜的物理损伤相结合。组织学上，这些病变表现为乳头瘤病毒感染的病理性改变，如异常增生细胞的凹陷细胞，一些异常增生或癌细胞的细胞核呈乳头瘤病毒属特异性抗原(GSA)阳性。此外，在这些细胞的核中还检测到了类似于乳头瘤病毒的病毒颗粒，其大小为50-55 nm。利用该动物模型，我们通过对该病毒基因组的分子克隆和测序，证明了一种新的仓鼠乳头瘤病毒的存在。基因组全序列分析证实为一种新的乳头状瘤病毒，命名为仓鼠口腔乳头瘤病毒(HOPV)。此外，我们还利用原位杂交技术在金黄地鼠舌上皮异型增生和恶性病变的细胞核中检测到了HOPV。计算机辅助系统发育分析显示，在基因组的不同区域，HOPV与其他乳头状瘤病毒具有不同的同源性。该病毒基因组全序列为7647bp，G+C含量为46.6%。这一大小与MnPV相似(7687个基点)。该基因组在一条链上有开放阅读框(ORF)，显示出通常的顺序：ORF E6、E7、E1、E2、L2和L1。ORF E2含有小的ORF E4。缺少ORF E5。这些克隆的基因组不同于其他啮齿动物乳头瘤病毒，如MMPV和MnPV，也不同于先前测序的动物和人乳头状瘤病毒基因组，因此，HOPV感染似乎是研究与乳头瘤病毒相关的粘膜癌变以及疫苗预防和恶性转化研究的良好模型。

项目成果

Maeda, H.: "Research on Effect of Chemical Carcinogen and Physical Wounding on Carcinogenesis."Oral Med Pathol. 4. 1-6 (1999)

Maeda, H.：“化学致癌物和物理损伤对致癌作用的研究。”口腔医学病理学。

Maeda,H.and Kameyama,Y.: "Research on Effect of Chemical Carcinogen and Physical Wounding on Carcinogenesis."Oral Med Pathol. 4. 1-6 (1999)

Maeda, H. 和 Kameyama, Y.：“化学致癌物和物理损伤对致癌作用的研究。”口腔医学病理学。