DIFFERENCES IN THE EXTENT OF INFLAMMATION CAUSED BY INTRATRACHEAL EXPOSURE TO 3 ULTRAFINE METALS - ROLE OF FREE-RADICALS

Nickel and cobalt, which belong to the same elemental group, are known to cause interstitial lung disease and bronchial asthma. The ability of these metals to injure lung cells and cause inflammation is likely to be important in their pathogenicity but comparative studies are rar e. Additionally, ultrafine (uf) forms of these metals are used increas ingly and their is little available information on their toxicity. Thu s the inflammatory response following intratracheal instillation of ul trafine particles of Co, Ni, and TiO2 was compared. Physiological sali ne (PS) was used as a vehicle control and DQ(12) quartz as a positive control. Male Wistar rats were intratracheally instilled with the 3 pa rticle types at a dose of 1 mg suspended in physiological saline. At 1 , 3, 7, 15, and 30 d after the injection, lung weight and the cellular and biochemical changes in bronchoalveolar lavage fluid (BALF) were d etermined. By all of the indices, Uf-Ni appeared to be the most injuri ous to the lung, causing severe and sustained inflammation, cytotoxici ty and increased epithelial permeability. The next most toxic material was DQ(12) quartz, with Uf-Co being closely similar in ability to cau se inflammation. Uf-TiO2 was more active than the saline control in al l of the indices, but was the least toxic of the particles studied. Th e present study reveals that three ultrafine particles of the same dia meter are dramatically different in their ability to cause inflammatio n. The three ultrafines were compared as to their ability to cause fre e-radical damage to supercoiled plasmid DNA, and the result of free-ra dical activity was found to be Uf-TiO2 much less than Uf-Co = Uf-Ni. D ifference in free-radical-generation activity therefore could underlie the difference in inflammation of these three ultrafine particle type s.