HAMSTER BRONCHIAL CARCINOGENESIS INDUCED BY CARCINOGEN-CONTAINING SUSTAINED-RELEASE IMPLANTS PLACED ENDOBRONCHIALLY - A CLINICALLY RELEVANTMODEL

For several widely appreciated reasons, the Syrian hamster has been th e most frequently used experimental animal in investigations of conduc ting airway carcinogenesis. To develop a model where bronchogenic canc er arises focally at a predetermined site, we used the Laskin-Kuschner self-retaining intrabronchial pellet principle, employing a carcinoge n-containing silastic polymer sustained release implant (SRI). The SRI is placed in the right lower lobe bronchus via tracheostomy; when mod ified, the SRI can be removed without loss of the animal. Special prep aration of the SRI implant site after fixation but prior to paraffin e mbedding allows for full histopathological examination of the carcinog en-affected target tissue. Logistic regression analysis of histologica l findings provides valid quantitative inter-regimen comparisons of hi stomorphic classifications suitable for determining modulation of carc inogenesis by external influences. Using this model, we demonstrated t hat the sequential progression of carcinogenesis (SPC) in hamster bron chus is similar to that which occurs in humans and in dogs, including both the ploidy increases that are progressive during the SPC, and the histological patterns of the induced cancers. We have shown genetic v ariation in susceptibility to carcinogenesis among inbred hamster stra ins, and have assessed effects of Bacillus Calmette-Guerin (BCG) immun ostimulation on the SPC. Time/dose response studies were performed, as were comparisons between four polycyclic aromatic hydrocarbon carcino gens. Systemic administration of 5-azacytidine (AZC) soon after SRI pl acement was found to inhibit the SPC, to alter the ploidy changes duri ng the SPC and in the eventual cancers, and to affect the degree of di fferentiation of the cancers. Studies using removable SRIs have assess ed the duration of carcinogen exposure required to induce a neoplastic transformation that proceeds to cancer without further carcinogen exp osure. Serial syngeneic transplantation of cancers arising in inbred a nimals has shown that the degree of tumor differentiation is affected by the extent of host immunocompetence, and has also led to developmen t of models for study of the processes of metastasis. (C) 1993 Wiley-L iss, Inc.