ADVERSE HEALTH-EFFECTS OF PM(10) PARTICLES - INVOLVEMENT OF IRON IN GENERATION OF HYDROXYL RADICAL

Objectives-Environmental particles < 10 mu m average aerodynamic diame ter (PM(10)) are associated with mortality, exacerbation of airways di seases, and decrement in lung function. It is hypothesised that PM(10) particles, along with other pathogenic particles, generate free radic als at their surface in reactions involving iron, and that this is a f actor in the pathogenicity of PM(10) particles. Identification of free radical activity in PM(10) and examination of the content and role of iron in this process was undertaken. Methods-Free radical activity wa s detected with a supercoiled plasmid, phi X174 RF1 DNA, and measured as scission of the supercoiled DNA (mediated by free radicals) by scan ning laser densitometry. The role of the hydroxyl radical was confirme d by the use of the specific scavenger mannitol, and the role of iron investigated with the iron chelator desferrioxamine-B (DSF-B). Iron re leased from PM(10) particles at pH 7.2 and pH 4.6 (to mimic conditions on the lung surface and in macrophage phagolysosomes, respectively) w as assessed spectrophotometrically with the Fe++ chelator ferrozine an d the Fe+++ chelator DSF-B. Results-PM(10) particles showed significan t free radical activity by their ability to degrade supercoiled DNA. A substantial part of this activity was due to the generation of hydrox yl radicals, as shown by partial protection with mannitol. Similarly, DSF-B also conferred protection against the damage caused to plasmid D NA indicating the role of iron in generation of hydroxyl radicals. Neg ligible Fe++ was released at either pH 7.2 or pH 4.6 by contrast with Fe+++, which was released in substantial quantities at both pHs, altho ugh twice as much was released at pH 4.6. Conclusions-PM(10) particles generate the hydroxyl radical, a highly deleterious free radical, in aqueous solution. This occurs by an iron dependent process and hydroxy l radicals could play a part in the pathogenicity of PM(10) particles. Iron release was greatest at the pH of the lysosome (pH 4.6) indicati ng that iron may be mobilised inside macrophages after phagocytosis, l eading to oxidative stress in the macrophages.