TUMOR-INDUCTION IN THE RODENT MASTOMYS-NATALENSIS BY ACTIVATION OF ENDOGENOUS PAPILLOMA-VIRUS GENOMES

TUMOR-INDUCTION IN THE RODENT MASTOMYS-NATALENSIS BY ACTIVATION OF ENDOGENOUS PAPILLOMA-VIRUS GENOMES
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DOI:
10.1038/308291a0
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发表时间:
1984-01-01
期刊:
影响因子:
64.8
通讯作者:
WAYSS, K
WAYSS, K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
AMTMANN, E;VOLM, M;WAYSS, K

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最近在疣状表皮发育不良患者的肿瘤1,2以及外阴癌和宫颈癌4,5中发现了来自人乳头瘤病毒的特定DNA序列,但乳头瘤病毒在这些肿瘤病因学中的作用尚不清楚。事实上,人们对良性乳头状瘤转化为恶性肿瘤的机制知之甚少,甚至不可能区分不活跃的乘客和参与肿瘤诱导的病毒。在这里,我们描述了一个动物系统,允许在分子水平上分析乳头状瘤病毒基因组与致癌物质的相互作用。在我们的mastomys natalensis(大鼠家族的近亲)群体中,我们发现染色体外乳头瘤病毒基因组持续存在于各种组织中,如皮肤、肌肉、肝脏和结肠。随着动物年龄的增长,皮肤细胞中病毒DNA的平均拷贝数增加,大约1岁时,乳突虫体内开始出现产生病毒的肿瘤。通过肿瘤启动子的慢性治疗,这一过程大大增强,并且已经发现病毒基因组的转录与肿瘤形成相关。
Specific DNA sequences from human papillomavirus have recently been detected in carcinomas from epidermodysplasia verruciformis patients1,2, and in vulvar3and cervical4,5carcinomas but the role of papilloma viruses in the aetiology of these tumours is unclear. Indeed, little is known about the mechanisms that convert benign papillomas into malignant tumours and it is not even possible to distinguish between inactive passengers and viruses involved in tumour induction. Here, we describe an animal system that permits an analysis of the interaction of papilloma virus genomes with carcinogenic agents at the molecular level. In our colony ofMastomys natalensis(a close relative of the rat family), we have found extrachromosomal papilloma virus genomes persisting in a variety of tissues such as skin, muscle, liver and colon. With the ageing of the animals, the average copy number of viral DNA in skin cells increases and virus-producing tumours begin to appear inMastomysat about 1 year old. This process is drastically enhanced by chronic treatment with a tumour promoter and transcription of the viral genomes has been found to be correlated with tumour formation.