ANALYSIS OF HUMAN TONSIL AND CANCER DNAS AND RNAS FOR DNA-SEQUENCES OF GROUP-C (SEROTYPES 1,2,5, AND 6) HUMAN ADENOVIRUSES
ANALYSIS OF HUMAN TONSIL AND CANCER DNAS AND RNAS FOR DNA-SEQUENCES OF GROUP-C (SEROTYPES 1,2,5, AND 6) HUMAN ADENOVIRUSES
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DOI：
10.1073/pnas.76.12.6606
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发表时间：
1979-01-01
影响因子：
11.1
通讯作者：
RIGDEN, P
中科院分区：
文献类型：
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作者：
GREEN, M;WOLD, WSM;RIGDEN, P
血清型1、2、5和6的C组人腺病毒（Ads）感染大多数儿童，并且通常引起淋巴组织的潜伏感染。广告将细胞转化为恶性样表型;致癌遗传信息位于病毒基因组左侧8%的HindIII-G DNA片段中。研究了C组Ad潜伏感染人扁桃体的分子基础以及这些病毒与人类癌症相关的可能性。扁桃体或癌DNA和RNA通过与体外标记的Ad 5 HindIII-G片段的液相饱和杂交来测定Ad序列。分析的52个扁桃体中约25%含有HindIII-G特异性的DNA或RNA序列，表明Ad转化序列在扁桃体中表达为RNA。4扁桃体DNA的Southern印迹分析揭示了多个拷贝的完整的Ad基因组在一个自由的状态，并提供了一个不寻常的形式的Ad基因组，可能的Ad DNA整合到细胞DNA的证据。在人类癌症的检测中，26例鳞状细胞癌（Cas）、3例腺癌、4例燕麦细胞癌、5例胃Cas、5例小肠Cas、15例结肠Cas、6例直肠Cas、5例霍奇金淋巴瘤和6例非霍奇金淋巴瘤以及2例乳腺Cas的DNA中未检测到Ad序列。重建实验表明，HindIII-G探针可以检测0.2-0.3%的病毒基因组的1个拷贝/细胞。在21例鳞状细胞癌、3例燕麦细胞癌、2例胃癌和18例结肠癌的RNA中未检测到HindIII-G特异性序列。在使用完整的Ad 2基因组作为探针的6个其他实验中，在灵敏度为λ的6个肺Cas、12个正常肺组织、33个胃肠道Cas、19个正常胃肠道组织、6个霍奇金淋巴瘤、3个乳腺Cas或4个肾Cas的DNA中没有发现Ad序列。1个拷贝/肿瘤细胞的5-10%的Ad 2基因组。所有Ad诱导的癌细胞应至少含有1-6%病毒基因组的1个拷贝，这是转化区域的最小尺寸，并且可能应含有更多基因组的多个拷贝。这些数据是反对C组广告是测试的癌症的原因的明确证据，其代表了。占美国癌症发病率的50%。在7例人类胎盘、12例正常肺或19例正常胃肠道组织的RNA中未检测到Ad 2序列（在44例癌症或23例扁桃体RNA中也未检测到Ad 2序列）。最近的一份关于人类胎盘RNA中存在Ad 2 RNA的报告未得到证实;不排除胎盘中一小部分细胞表达C组相关序列的可能性。
Group C human adenoviruses (Ads) of serotypes 1, 2, 5 and 6 infect most children and commonly cause latent infections of lymphoid tissues. Ads transform cells into a malignant-like phenotype; the oncogenic genetic information is in the left 8% of the viral genome, in the HindIII-G DNA fragment. The molecular basis for group C Ad latent infections in human tonsils and the possibility of these viruses are linked to human cancer were investigated. Tonsil or cancer DNAs and RNAs were assayed for Ad sequences by liquid-phase saturation-hybridization with in vitro-labeled Ad5 HindIII-G fragment. About 25% of the 52 tonsils analyzed contained DNA or RNA sequences specific to HindIII-G, indicating that Ad transforming sequences are expressed as RNA in tonsils. Southern blotting analysis of 4 tonsil DNA revealed multiple copies of the complete Ad genome in a free state and provided evidence for an unusual form of the Ad genome, possibly Ad DNA integrated into cellular DNA. In assays of human cancers, no Ad sequences were detected in DNAs from 26 squamous cell carcinomas (Cas), 3 adenocarcinomas, 4 oat cell Cas, 5 stomach Cas, 5 small intestine Cas, 15 colon Cas, 6 rectum Cas, 5 Hodgkin and 6 non-Hodgkin lymphomas and 2 breast Cas. Reconstruction experiments indicated that the HindIII-G probe could detect 1 copy/cell of 0.2-0.3% of the viral genome. No HindIII-G-specific sequences were detected in RNA from 21 squamous cell Cas, 3 oat cell Cas, 2 stomach Cas, or 18 colon Cas. In 6 other experiments using the complete Ad2 genome as probe, no Ad sequences were found in DNAs from 6 lung Cas, 12 normal lung tissues, 33 gastrointestinal Cas, 19 normal gastrointestinal tissues, 6 Hodgkin lymphomas, 3 breast Cas, or 4 kidney Cas, at a sensitivity of .apprx. 1 copy/tumor cell of 5-10% of the Ad2 genome. All Ad-induced cancer cells should contain at least 1 copy of 1-6% of the viral genome, the minimal size of the transforming region, and probably should contain multiple copies of more of the genome. The data are definitive evidence against group C Ads being the cause of the cancers tested, which represent .apprx. 50% of the cancer incidence in the USA. Ad2 sequences were not detected in RNA from 7 human placentas, 12 normal lungs, or 19 normal gastrointestinal tissues (nor in 44 cancer or 23 tonsil RNA). A recent report of the presence of Ad2 RNA in RNA from human placentas was not confirmed; the possibility that a small population of cells in placenta expresses group C related sequences is not ruled out.