DNA damage and inflammation in the rat quartz model: Differences in inflammatory response and formation of oxidative DNA adducts to high and low doseof DQ12 quartz

Chronic exposure to poorly soluble particles such as quartz and diesel soot produces dose-dependent inflammatory responses in the rat lung. it has bee n shown that the inflammation in the rat lung causes persistent oxidative D NA damage and mutations in proliferation-competent cells, which are thought to be critical for tumorigenesis. in measuring various inflammatory parame ters to a multidose quartz exposure in parallel with the amount of 8-oxogua nine (8-oxo-Gua) on the cellular level in rat lung mechanistic data for und erstanding the underlying processes could be gained. Rat lungs (female Wist ar, 180-220 g/bodyweight) were instilled with quartz DQ12 (doses 0.3, 1.5, and 7.5 mg/animal; controls: corundum at the same doses and physiological N aCl) and analyzed 90 days after intratracheal instillation. The bronchoalve olar lavage (BAL) fluid was determined for inflammation markers (differenti al cell count, protein, lung surfactant lipids, and tumor necrosis factor a lpha); tissue sections of lungs were investigated for the amount of 8-oxoGu a on the cellular level using an antibody against 8-oxoGua. The results ref lect different responses for quartz versus all controls and shaw a clear do se-response relationship Quartz elicited inflammatory reponses determined i n the BAL fluid even at the low dose (0.3 mg/animal). In contrast the level of 8-oxoGua in the lung of animals exposed to 0.3 mg quartz iras not stati stically increased above controls, whereas doses of 7.5 mg and 7.5 mg cause d significant elevations. The data obtained indicate a no-effect level for the persistence of the mutagenic DNA adduct 8-oxoguanine in the epithelial lung cells at a low-dose quartz exposure that is still inflammatoric and fi brogenic.