REGRESSION OF BRONCHIAL EPITHELIAL CANCER IN HAMSTERS

For bronchogenic carcinoma, if and when the sequential process of carc inogenesis is reversible is fundamental to chemoprevention research. I n our hamster model, focally originating non-small cell lung carcinoma (NSCLC) develops via a reproducible sequential process of carcinogene sis by 180 days after endobronchial sustained-release implants (SRIs) of 10% benzo(a)pyrene. In this study, 114 hamsters received removable 10% benzo(a)pyrene SRIs. Short-term controls were sacrificed in 3 grou ps at 50, 65, and 80 days after SRI placement. Three experimental grou ps had SRIs removed at 50, 65, and 80 days after placement, and sacrif ice was delayed until 100 to 180 days later. Long-term controls retain ed SRIs until sacrifice at 180 or 240 days after SRI placement. All lo ng-term controls had NSCLC. Preneoplastic change was more common in 50 - and 65-day controls, as compared with hamsters with equal duration o f SRI exposure whose sacrifice was delayed until 100 to 180 days after SRI removal (p < 0.05). The 56% incidence of early NSCLC in hamsters sacrificed after 80 days of SRI exposure decreased to 5% in hamsters t hat had delayed sacrifice after SRI removal after 80 days of exposure. At the 10% benzo(a)pyrene dose used, hamster bronchial epithelium req uires more than 80 days of continuous exposure to become irreversibly committed to NSCLC uniformly. Microinvasive NSCLC in hamsters often re gresses, and it is not necessarily a precursor of overt invasive cance r. The removable SRI model provides new opportunities to evaluate chem oprevention of NSCLC and the related molecular-genetic control mechani sms.