Abstract
In the rat model of fibrosis-associated lung cancer induced by crystalline silica, carcinomas derived from alveolar type II cells are the most common tumor type. To investigate the mechanisms responsible for crystalline silica effects on alveolar epithelial cells, we have studied the toxicity of α-quartz to the fetal rat lung epithelial cell line, FRLE. Chemical modification of quartz surface was obtained by treating the α-quartz sample Mil-U-Sil 5 (MQZ) with poly(2-vinylpyridine-N-oxide) (2-PVPNO) and poly(4-vinylpyridine-N-oxide) (4-PVPNO). 2-PVPNO and 4-PVPNO were shown to bind to the MQZ surface (3.2 ± 0.1 μg/mg MQZ for 2-PVPNO and 3.4 ± 0.7 μg/mg MQZ for 4-PVPNO, respectively). In the cytotoxicity assay, FRLE cells were plated in minimum essential medium (MEM) with 10 percent fetal bovine serum (FBS); after 24 hours the medium was changed to MEM/1 percent FBS containing either MQZ or anatase at doses from 1.5 to 100 μm/cm2 dish surface area. After 24 hours the medium was changed to MEM/10 percent FBS and the cells were fixed and stained 4 days later. Toxicity was calculated as the proportion of cells that survived to form colonies, or colony-forming efficiency (CFE). MQZ induced marked dose-dependent toxicity (CFE, as percentage of untreated control, was 71.1% at 3.1 μg/cm2, 57.8% at 12.5 μg/cm2, and 0 at 100 μm/cm2). Anatase showed much lower toxicity (CFE was 66.6% at 100 μg/cm2). 2-PVPNO and 4-PVPNO at 10 μg/ml both markedly reduced MQZ quartz toxicity [% CFE after MQZ (100 μg/cm2) + 2-PVPNO was 48.2% and after MQZ (100 μm/cm2) + 4-PVPNO was 50.6%]. Ultraviolet spectrometry showed that 2-PVPNO and 4-PVPNO adsorb to the quartz surface but not to anatase. Fourier transform infrared spectrometry revealed hydroxyl groups on the quartz surface, but no detectable hydroxyl groups on the anatase surface. These results imply that hydrogen binding of silanol groups is involved in quartz toxicity to alveolar epithelial cells, and that 2-PVPNO and 4-PVPNO have comparable effects in preventing quartz toxicity. Mao, Y.; Daniel, L.N.; Knapton, A.D.; Shi, X.; Saffiotti, U.: Protective Effects of Silanol Group Binding Agents on Quartz Toxicity to Rat Lung Alveolar Cells. Appl. Occup. Environ. Hyg. 10(12):1132–1137; 1995.
