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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crystalline silica (quartz) induces silicosis and associated peripheral lung carcinomas in rats. The role and pattern of expression of transforming growth factor (TGF)-beta1/beta2 mRNA transcripts were investigated in the fetal rat lung epithelial cell line FRLE, its neoplastic transformants and derived tumors in athymic nude mice. FRLE cells, treated with 100 microgram/cm2 of quartz in serum-free medium, gave rise to phenotypically altered, tumorigenic cells. Quartz-treated, transformed and tumorigenic cells, subcultured directly (QTT-C1) or after growth in soft agar (QTT-C2), formed tumors in athymic nude mice (QTT-T1). Cells subcultured from the tumors (QTT-T1C) were also tumorigenic in nude mice (QTT-T2). QTT-T1 and QTT-T2 tumors were poorly differentiated carcinomas with variable amounts of extracellular matrix-associated TGF-beta1 and desmoplasia. For comparison, a tumorigenic cell line derived from FRLE cells transformed with a mutated K-ras plasmid (RT-C1) and cells subcultured from a corresponding nude mouse tumor (RT-T1) and designated RT-T1C were used. Whereas TGF-beta1 and TGF-beta2 inhibited the growth of QTT-T1C and FRLE cells in a dose-dependent fashion, RT-T1C cells, containing an activated ras gene, were relatively unaffected. TGF-beta1 and TGF-beta2 mRNAs were expressed at higher levels in QTT-T1C cells than in FRLE and TR-T1C cells, and there was an increase in TGF-beta type II receptor (TGR-betaR) mRNA expression in QTT-T1C and RT-T1C cells compared to FRLE cells. Carcinomas in nude mice derived from QTT and RT cells and silicosis-associated lung carcinomas induced in rats by intra-tracheal quartz did not express either active or latent forms of TGF-beta1 protein on immunohistochemistry. The disparity between TGF-beta1 mRNA and TGF-beta1 protein expression in QTT tumors may be due to post-transcriptional regulation of TGF-beta1.
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PMID:Transforming growth factor beta expression and transformation of rat lung epithelial cells by crystalline silica (quartz). 859 16

Hepatic silicosis, cirrhosis, liver cell adenoma, and carcinomas developed in nude mice (NCr-Nu) given quartz by the subcutaneous and intraperitoneal routes. Syrian golden hamsters (15:16 EHS:cr) given quartz by both routes developed extensive fibrosis and cirrhosis and had higher morbidity and mortality rates after 3 months. Crystalline silica (quartz) induces fibrosis, adenomas, and carcinomas in the lungs of Fisher 344 rats, but certain strains of mice and hamsters are resistant to quartz-induced pulmonary carcinogenesis. Pulmonary fibrosis, however, is minimal in mice and absent in hamsters who received quartz intratracheally. To determine whether species differences are due to organ-specific rather than species-specific factors, susceptibility of the liver to quartz toxicity was investigated in nude mice and hamsters. The present study shows that the differential manifestations of quartz toxicity by these rodent species are dependent on factors that are organ-specific rather than host-specific. At 3 months, hepatocytes in mice were immunostained with intracellular transforming growth factor (TGF) beta 1 (LC 1-30) but not with TGF-beta 1 latency-associated peptide (LAP) protein (266-278); at 12 months, hepatocytes were immunostained with TGF-beta 1 LAP (266-278) but not with TGF-beta 1 (LC1-30). The hepatocytes of hamsters at 3 months showed immunoreactivities to TGF-beta 1 LAP (266-278) and TGF-beta 1 (LC1-30); immunostaining to TGF-beta 1 (LC1-30) was detected in nonparenchymal cells. Extracellular TGF-beta 1 (CC1-30) was detected in the silicotic granulomas and fibrous tissue in livers of both species. Quartz-induced liver carcinoma did not express TGF-beta 1 LAP (266-278) and LC (1-30) proteins, but these were detected in the cells of the adenoma in the same liver. Control animals showed no hepatic lesions nor immunoreactivity to TGF-beta 1. The spatial and temporal patterns of expression of TGF-beta 1, TGF-beta 2, TGF-beta receptor type II messenger RNAs (mRNAs), and TGF-beta 1 proteins in the different hepatic lesions suggests that TGF-beta isoforms may play a role in the pathogenesis of quartz-induced fibrosis, cirrhosis, liver cell adenoma, and carcinoma.
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PMID:Hepatic silicosis, cirrhosis, and liver tumors in mice and hamsters: studies of transforming growth factor beta expression. 862 Nov 63