Wold W S, Mackey J K, Rigden P, Green M
Cancer Res. 1979 Sep;39(9):3479-84.
We have investigated whether Group B human adenoviruses (Ad) (Ad3, Ad7, Ad11, Ad14, Ad16, and Ad21), which are widespread in the human population and are tumorigenic in hamsters, may play a role in human cancer. Hybridization of Ad7-radiolabeled DNA with DNA's from an Ad7-induced primary hamster tumor and from two cell lines (5728 and Ad7 P-cell) established from Ad7-induced hamster tumors indicated multiple copies per cell of 17, 30 to 36, and 20%, respectively of the Ad7 genome. Thus, cells transformed by Group B Ads resemble cells transformed by Group C and Group A Ad's in that they retain multiple copies of a variable fraction of the viral genome. These model studies suggest that possible Group B Ad-induced human cancer cells should contain one or more copies of virus DNA per cell. Therefore, we assayed human cancer DNA's for Ad sequences, by highly sensitive "saturation-hybridization" reactions with Ad7 or Ad11 DNA (4 X 10(6) to 2.1 x 10(8) cpm/microgram). We concentrated on cancers of the respiratory and digestive systems, because these systems are the most common sites of infection by Group B Ad's. In 8 independent experiments, no Ad7 sequences were detected in DNA's from 16 normal lung tissues, 18 normal tissues of the digestive system, 34 cancers of the respiratory system, 19 cancers of the digestive system, 11 cancers of the urinary system, 5 cancers of the genital system, 3 cancers of the breast, and 6 Hodgkin's lymphomas. Reconstruction controls with added Ad7 DNA indicated that about 0.05 to 0.1 copy of Ad7 DNA per cell should be detected. Ad11 is strongly implicated as a cause of acute hemorrhagic cystitis. In two independent experiments, no Ad11 sequences were detected in DNA's from 9 carcinomas of bladder, 10 carcinomas of prostate, 24 carcinomas of kidney, 3 hypernephromas, 3 Wilms' tumors, or 2 normal kidneys. Reconstruction experiments indicated that the cancer DNA assays had a sensitivity of 0.05 to 0.1 copy of Ad11 DNA per cell. The DNA's of Group B Ad's are greater than 85% homologous by hybridization; thus, these results are applicable to all Group B serotypes. Our data provide evidence (but not formal proof) that none of the human cancers that we analyzed were induced by Group B Ad's. These tumors represent about 50% of the tumors that affect humans. The possible involvement of Group B Ad's in other less common forms of human cancers is under investigation in our laboratory.
我们研究了B组人类腺病毒（Ad）（Ad3、Ad7、Ad11、Ad14、Ad16和Ad21），这些病毒在人群中广泛传播且在仓鼠中具有致瘤性，它们是否可能在人类癌症中发挥作用。用放射性标记的Ad7 DNA与来自Ad7诱导的原发性仓鼠肿瘤以及从Ad7诱导的仓鼠肿瘤建立的两个细胞系（5728和Ad7 P细胞）的DNA进行杂交，结果表明每个细胞分别有17、30至36个拷贝以及Ad7基因组的20%。因此，由B组腺病毒转化的细胞类似于由C组和A组腺病毒转化的细胞，因为它们保留了病毒基因组可变部分的多个拷贝。这些模型研究表明，可能由B组腺病毒诱导的人类癌细胞每个细胞应含有一个或多个病毒DNA拷贝。因此，我们通过与Ad7或Ad11 DNA（4×10⁶至2.1×10⁸ cpm/μg）进行高度敏感的“饱和杂交”反应，检测人类癌症DNA中的腺病毒序列。我们专注于呼吸系统和消化系统的癌症，因为这些系统是B组腺病毒最常见的感染部位。在8个独立实验中，在16个正常肺组织、18个消化系统正常组织、34个呼吸系统癌症、19个消化系统癌症、11个泌尿系统癌症、5个生殖系统癌症、3个乳腺癌和6个霍奇金淋巴瘤的DNA中未检测到Ad7序列。添加Ad7 DNA的重建对照表明，每个细胞应能检测到约0.05至0.1个Ad7 DNA拷贝。Ad11被强烈认为是急性出血性膀胱炎的病因。在两个独立实验中，在9个膀胱癌、10个前列腺癌、24个肾癌、3个肾上腺瘤、3个肾母细胞瘤或2个正常肾脏的DNA中未检测到Ad11序列。重建实验表明，癌症DNA检测的灵敏度为每个细胞0.05至0.1个Ad11 DNA拷贝。B组腺病毒的DNA通过杂交具有大于85%的同源性；因此，这些结果适用于所有B组血清型。我们的数据提供了证据（但不是正式证明），表明我们分析的人类癌症中没有一种是由B组腺病毒诱导的。这些肿瘤约占影响人类的肿瘤的50%。B组腺病毒在其他不太常见的人类癌症形式中的可能参与情况正在我们实验室进行研究。
