Benfield J R, Hammond W G
Department of Surgery, University of California, Davis School of Medicine 95616.
Cancer Res. 1992 May 1;52(9 Suppl):2687s-2693s.
Models of the sequential process of lung carcinomas have been developed in dogs and hamsters. The bronchial mucosa, or the pulmonary parenchyma, was exposed at selected focal sites to polycyclic aromatic hydrocarbons [most often benzo(a)pyrene or methylcholanthrene]. In hamsters, sustained release implants that contained carcinogen were implanted into the right lower lobe bronchus. In dogs, for orthotopic carcinogenesis the carcinogens were repeatedly injected into the bronchial submucosa or topically applied to the bronchus; sustained release implants were implanted into the pulmonary parenchyma. Heterotopic focal canine bronchial carcinogenesis was accomplished by exposing s.c. bronchial autografts (8-12/dog) to methylcholanthrene. In both species a predictable, reproducible, preneoplastic continuum that leads to bronchial squamous cell carcinoma that metastasizes has been characterized; serial measurements of total cellular DNA showed that ploidy increased in proportion to the stage of preneoplasia. In both species there were adenocarcinomas, including bronchiolar (bronchioloalveolar) carcinomas and other varieties of non-small cell cancers. Different susceptibility to carcinogenesis has been demonstrated among different inbred strains of hamsters; 58% of cancers were adenocarcinomas in one strain. From these models, specimens that are not readily available from humans can be obtained for the study of cellular events during lung carcinogenesis. In parallel with studies in humans, these animal models can be used to evaluate methods of possible chemoprevention and early detection.
已在犬类和仓鼠身上建立了肺癌连续发生过程的模型。在选定的局部部位，将支气管黏膜或肺实质暴露于多环芳烃（最常见的是苯并(a)芘或甲基胆蒽）。在仓鼠中，将含有致癌物的缓释植入物植入右下叶支气管。在犬类中，对于原位致癌，将致癌物反复注射到支气管黏膜下层或局部应用于支气管；将缓释植入物植入肺实质。通过将皮下支气管自体移植物（每只犬8 - 12个）暴露于甲基胆蒽来实现异位局部犬支气管致癌。在这两个物种中，已经明确了一个可预测、可重复的癌前连续过程，该过程会导致发生转移的支气管鳞状细胞癌；对总细胞DNA的系列测量表明，倍体与癌前病变阶段成比例增加。在这两个物种中都有腺癌，包括细支气管（细支气管肺泡）癌和其他类型的非小细胞癌。已证明不同近交系仓鼠对致癌作用的易感性不同；在一个品系中，58%的癌症为腺癌。从这些模型中，可以获取人体难以获得的标本，用于研究肺癌发生过程中的细胞事件。与人体研究并行，这些动物模型可用于评估可能的化学预防和早期检测方法。
