Protective effects of silanol group binding agents on quartz toxicity to ratlung alveolar cells

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 havestudied the toxicity of a-quartz to the fetal rat lung epithelial cell line, FRLE. Chemical modification of quartz surface was obtained bytreating the a-quartz sample Mil-U-Sil 5 (MQZ) with poly(2-vinylpyridine-JV-oxide) (2-PVPNO) and poly(4-vinylpyridine-N-oxide) (4-PVPNO). 2-PVPNO and 4-PVPNO were shown to bindto the MQZ surface (3.2 ± 0.1 pig/mg MQZ for 2-PVPNO and 3.4± 0.7 pig/mg MQZ for 4-PVPNO, respectively). In the cytotoxicityassay, FRLE cells were plated in minimum essential medium (MEM)with 10 percent fetal bovine serum (FBS); after 24 hours the mediumwas changed to MEM/1 percent FBS containing either MQZ oranatase at doses from 1.5 to 100 /im/cm2 dish surface area. After 24hours the medium was changed to MEM/10 percent FBS and thecells were fixed and stained 4 days later. Toxicity was calculated as theproportion of cells that survived to form colonies, or colony-formingefficiency (CFE). MQZ induced marked dose-dependent toxicity(CFE, as percentage of untreated control, was 71.1% at 3.1 fig/cm2,57.8% at 12.5 pig/cm2, and 0 at 100 pim/cm2). Anatase showed muchlower toxicity (CFE was 66.6% at 100 pig/cm2). 2-PVPNO and4-PVPNO at 10 pig/ml both markedly reduced MQZ quartz toxicity[% CFE after MQZ (100 ftg/cm2) + 2-PVPNO was 48.2% and afterMQZ (100 pun/cm2) + 4-PVPNO was 50.6%]. Ultraviolet spectrometry showed that 2-PVPNO and 4-PVPNO adsorb to the quartzsurface but not to anatase. Fourier transform infrared spectrometryrevealed hydroxyl groups on the quartz surface, but no detectablehydroxyl groups on the anatase surface. These results imply that hydrogen binding of silanol groups is involved in quartz toxicity toalveolar epithelial cells, and that 2-PVPNO and 4-PVPNO havecomparable effects in preventing quartz toxicity.