Bronchial and pulmonary carcinogenesis at focal sites in dogs and hamsters

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.