Tobacco-borne siderophoric activity.

The proinflammatory and carcinogenic effects of cigarette smoking are well known. Recent evidence indicts iron as a powerful promoter of inflammatory processes and, perhaps not coincidentally, the lungs and alveolar macrophages of smokers contain abnormally large amounts of iron. Furthermore, ferruginous compounds such as asbestos exert a powerful synergy with smoking in the causation of pulmonary neoplasia. Indeed, elements in tobacco smoke and asbestos synergistically damage DNA through reactions mediated by the (probably iron-dependent) formation of hydroxyl radical. These considerations prompted the hypothesis that tobacco smoke might contain substances capable of "delocalizing' iron. We find that one or more substances in organic extracts of smoke and unburned tobacco will transfer iron from an aqueous to an immiscible organic phase. This organic solvation requires the prior reduction of iron which can be effected by elements in smoke extracts. The translation of iron into organic phase is dependent on time and on the concentration of iron within the aqueous phase. Organic condensates of smoke will leach iron from rich forms of asbestos (amosite and crocidolite). Perhaps most importantly, exposure of intact human cells (erythrocytes) to dried residues of such condensates causes the accumulation of iron. This iron is evidently intracellular because it is inaccessible to powerful extracellular iron chelator such as deferoxamine. This tobacco-borne siderophoric activity may help explain some of the pathologic consequences of tobacco use as pulmonary inflammation and neoplasia.