PULMONARY ALVEOLAR PROTEINOSIS IN RATS AFTER ADMINISTRATION OF QUARTZ- ITS POSSIBLE ROLE IN MORPHOGENESIS OF LUNG-CANCER

In rats, primary peripheral lung tumors composed predominantly of alve olar type II cells have been induced by inhalation of alpha quartz. In our retrospective study on proliferation markers we evaluated lung sp ecimens of 140 Wistar rats from larger experiments, which had been exp osed to Dorentrup quartz (DQ12) by inhalation (10 mg/m3, 56 Weeks, 5 d ays/week, 7 h/day: n=27) or intratracheal instillations (5 mg: n=38; 2 0 mg: n=10; 50 mg: n=28; 15x3 mg: n=12). In the last group 8/12 animal s developed lung tumors. Animals were sacrificed 1-32 months after adm inistration. For identification of an increased proliferation of alveo lar type II cells the DNA content was monitored by microscopic (static ) cytophotometry in histological slides. The argyrophil (AgNOR) method for the demonstration of nucleolar organizer regions (NOR) was used a s second marker of type II cell proliferation. Measurements made 24 mo nths after inhalation of DQ12 showed a slight increase of pneumocytic proliferation with 1.64+/-0.14 AgNOR/nucleus compared to the controls (1.23+/-0.04 mean AgNOR/nucleus). After intratracheal instillation of DQ12 a significant increase of AgNOR was found, e.g. 5 mg: 1.93+/-0.23 AgNOR/nucleus (6 months) and 1.96+/-0.19 (12 months); 50 mg: 1.77+/-0 .15 (6 months) and 2.18+/-0.05 (12 months)-. 15x3 mg (+2 ml 2% polyvin ylpyridine N-oxide s.c.): 1.81+/-0.13 AgNOR/nucleus (27-32 months). Wi th the aid of the 2 c deviation index, i.e. the mean square deviation from the diploid DNA value, it was possible also to identify the patho logically increased proliferation of type II cells after intratracheal instillation of quartz: 0.02+/-0.01-0.06+/-0.04 c2 (controls); 0.07+/ -0.04 c2 (5 mg/12 months); 0.12+/-0.08 c2 (15x3 mg/>27 months) and 0.6 8+/-0.48 c2 (50 mg/12 months). Only in the last group were nearly trip loid values detected. Summarizing our results, intratracheal instillat ion and inhalation of quartz in rats regularly induces alveolar protei nosis and interstitial fibrosis in combination with a dose- and time-d ependent increase of the type II cell proliferation rate. As mitogenes is increases carcinogenesis, alveolar proteinosis with increased pneum ocytic proliferative activity might be a prerequisite for enhanced tum or development.