A) Histopathology. Further studies were made of the cellular reactions induced by a single intratracheal instillation of Min-U-Sil 5 quartz (MQZ) or of hydrofluoric-acid-etched MQZ in F344 rats, using tissues from previously conducted lifetime and serial sacrifice experiments. These studies resulted in the induction of high incidences of peripheral lung carcinomas, derived from hyperplastic areas of alveolar type II epithelium, adjacent to silicotic granulomas. The cellular reaction to silica had previously been found to be markedly different in three tested species. Rats develop typical silicotic granulomas and adjacent epithelial alveolar hyperplasia and, eventually, high incidences of lung carcinomas (mostly adenocarcinomas); mice develop silicosis but no persistent epithelial hyperplasia and no tumors; hamsters develop macrophagic storage lesions but no progressive fibrosis and no epithelial proliferation. Further histological observations of human lungs with silicosis and lung cancer showed similarities with two of the lesions observed in the experimental silica-treated rats, namely, (a) adenocarcinoma growing among fibrotic tissue and around it (""""""""scar cancer""""""""); and (b) epithelial hyperplasia and proliferative lesions adjacent to silicotic granulomas, in areas distant from the carcinoma. (B) Molecular biology. Formalin-fixed, paraffin-embedded rat lungs containing silica-induced carcinomas were sectioned and the areas with carcinoma were carefully excised, subjected to DNA extraction, and processed by the polymerase chain reaction method for amplification of selected genes. The p53 tumor suppressor gene is currently being investigated, using a pair of p53 rat primers specific for exons 4-8. The amplified products are subjected to electrophoresis in 0.8% agarose gel and stained with ethidium bromide; the p53 gene expressions are sequenced and their mutation frequencies calculated.
