The role of chronic pulmonary granulomatosis/fibrosis in the induction of lung cancer was studied in a new experimental model, i.e., carcinogenesis by silica. Crystalline silica forms (quartz, hydrofluoric-acid-etched quartz, cristobalite and tridymite) in fine particles were instilled intratracheally in inbred rats, hamsters and mice. Long-term studies with quartz and hydrofluoric- acid-etched quartz showed that rats developed high incidences of pulmonary carcinomas (mostly adenocarcinomas) with prevalence in females. Serial sacrifice studies showed that this carcinogenic response of the rat is preceded by an intense hyperplasia of the bronchiolar and alveolar (type 11) epithelia in areas adjacent to silicotic granulomatous lesions. The epithelial hyperplasia begins within days of single administrations of silica and progresses into proliferative hyperplasias and adenomatoid lesions, and ultimately into carcinomas. In contrast, the epithelial reaction was minimal in hamsters and transient in mice. Within the times so far observed, no carcinogenic response was found in the lungs of hamsters and mice, even in the adenoma-prone strain A. Marked species differences were identified in the structure and cellular composition of the granulomatous reaction. The correlation of epithelial proliferation with the adjacent inflammatory cells and their mediators is investigated in relation to host differences in the cellular pathogenesis of the epithelial and inflammatory/fibrogenic responses. Dimethylsulfoxide (DMSO), given intraperitoneally, markedly enhanced respiratory carcinogenesis by intratracheal benzo(a)pyrene/ferric oxide (BP) in hamsters. The enhancement was higher when DMSO was given concurrently rather than five days after each BP dose. Autoradiographic analysis showed no influence of concurrent DMSO on localization and binding of a single BP dose in the whole respiratory tract.
