Campo M S, O'Neil B W, Barron R J, Jarrett W F
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, UK.
Carcinogenesis. 1994 Aug;15(8):1597-601. doi: 10.1093/carcin/15.8.1597.
Bovine papillomavirus type 4 (BPV-4) is the aetiological agent of epithelial papillomas of the upper alimentary canal in cattle. These benign tumours can become a focus for transformation to squamous cell carcinomas in animals feeding on bracken fern. Strong epidemiological evidence suggests that the progression to malignancy is due to the interplay between BPV-4 and mutagenic and immunosuppressing chemicals present in the fern. The carcinomas of the upper alimentary canal are often accompanied by adenomas and adenocarcinomas of the lower intestine and bracken-grazing animals are also heavily immunosuppressed. To elucidate the individual roles and the concerted action of the viral and chemical factors involved in tumorigenesis and malignant conversion, we attempted to reproduce experimentally the cancer syndrome observed in the field. Florid persistent papillomatosis of the upper alimentary canal was reproduced in animals infected with BPV-4 and immunosuppressed either by a diet of bracken or by treatment with azathioprine; cancer of the upper alimentary tract or of the lower intestine developed only in animals infected with virus and fed on bracken fern. As in field cases, BPV-4 DNA was detected in papillomas but not in cancers. We conclude that immunosuppression is necessary for persistence and spread of viral papillomas, that the fern mutagens are responsible for neoplastic conversion of papilloma cells, and that continuous expression of viral functions is not required for the maintenance of the malignant state.
牛乳头瘤病毒4型（BPV-4）是牛上消化道上皮乳头瘤的病原体。这些良性肿瘤在以蕨菜为食的动物中可能会成为鳞状细胞癌的转化病灶。有力的流行病学证据表明，恶性进展是由于BPV-4与蕨菜中存在的诱变和免疫抑制化学物质之间的相互作用所致。上消化道癌常伴有下肠道的腺瘤和腺癌，而且食用蕨菜的动物也会受到严重的免疫抑制。为了阐明病毒和化学因素在肿瘤发生和恶性转化中的各自作用及协同作用，我们试图通过实验重现野外观察到的癌症综合征。给感染BPV-4并通过蕨菜饮食或硫唑嘌呤治疗进行免疫抑制的动物接种，再现了上消化道的明显持续性乳头瘤病；只有感染病毒并以蕨菜为食的动物才会发生上消化道或下肠道癌症。与野外病例一样，在乳头瘤中检测到BPV-4 DNA，但在癌症中未检测到。我们得出结论，免疫抑制对于病毒乳头瘤的持续存在和传播是必要的，蕨菜诱变剂是乳头瘤细胞肿瘤转化的原因，并且维持恶性状态不需要病毒功能的持续表达。
