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

在以前的研究中，我们开发了一个高度可重复的致癌模型相结合的DMBA应用与仓鼠舌粘膜的物理创伤。组织学上，这些病变表现出指示乳头瘤病毒感染的病理特征性变化，如发育不良细胞的挖空细胞，并且一些发育不良或癌细胞的细胞核对乳头瘤病毒属特异性抗原（GSA）呈阳性。此外，在这些细胞的细胞核中检测到类似于乳头瘤病毒的病毒颗粒，其直径为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实了一种新的仓鼠乳头瘤病毒的存在。经全序列分析证实，该病毒为一种新型乳头瘤病毒，命名为仓鼠口腔乳头瘤病毒（HOPV）。此外，我们还用原位杂交技术在金黄地鼠舌上皮的不典型增生和恶性病变的细胞核中检测到HOPV。计算机辅助系统发育分析显示，HOPV与其他乳头瘤病毒在基因组的不同区域具有不同的同源性。该病毒基因组全长7647 bp，G+C含量为46.6%。该大小与MnPV（7687 bp）的大小相似。该基因组在一条链上具有开放阅读框（ORF），显示通常的顺序：ORF E6、E7、E1、E2、L2和L1。ORF E2包含小ORF E4。ORF E5缺失。这些克隆的基因组不同于其他啮齿类乳头瘤病毒，如MmPV和MnPV，也不同于先前测序的动物和人乳头瘤病毒的基因组。因此，HOPV感染似乎是一个很好的模型，研究粘膜癌与乳头瘤病毒和疫苗预防和预防或治疗恶性转化的研究。

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.