Pepper C, Jasani B, Navabi H, Wynford-Thomas D, Gibbs A R
Department of Haematology, Llandough Hospital, NHS Trust, Penarth, South Glamorgan, UK.
Thorax. 1996 Nov;51(11):1074-6. doi: 10.1136/thx.51.11.1074.
DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in man though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe. The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period.
DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues-namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively.
PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma. In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers. The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other.
Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.
在美国、意大利和德国近期的大部分胸膜间皮瘤新鲜冷冻组织中，已鉴定出与猿猴病毒40转化因子、大T抗原和小t抗原（SV40LTAg）相关的DNA序列及免疫反应性，提示存在病因学联系。SV40通常对人类无感染性，但其可在组织培养中转化人类细胞。1959年至1961年间，西方大量人群因接种受污染的脊髓灰质炎疫苗而意外经肠道外途径接种了活SV40，这可能是美国、英国和欧洲间皮瘤发病率持续上升的一个因素。本研究调查了英国近期诊断的间皮瘤病例中SV40LTAg DNA的存在情况，以及检测存档组织中SV40 DNA以对疫苗接种期间病例进行回顾性分析的可行性。
从9例近期诊断的间皮瘤、9例肺腺癌和3例反应性胸膜的新鲜冷冻和/或复水的福尔马林固定石蜡包埋组织切片中提取DNA，并使用先前用于新鲜冷冻组织的引物对通过聚合酶链反应（PCR）进行扩增，即针对SV40特有的LTAg基因序列的SV引物组，以及分别针对SV40与乳头瘤病毒BK和JC株共有的序列的PYV引物组。
SV引物组的PCR阳性仅限于9例间皮瘤中的4例。相比之下，9例间皮瘤中的6例、9例腺癌中的2例和3例反应性胸膜中的1例对PYV引物呈阳性。新鲜冷冻组织与相应的福尔马林固定石蜡包埋组织的结果相互吻合良好。
我们的数据为英国人群中SV40LTAg引物特异性DNA与人类肺间皮瘤的关联提供了证据。
