TOXICITY OF TRACE-ELEMENTS IN TOBACCO-SMOKE

The potential to cause cellular damage by metal ions in conjunction wi th other constituents of tobacco smoke is enormous. Various studies ha ve demonstrated the role of reactive oxygen species in the toxicity of transition metals, and the presence of many highly reactive metal ion s in high concentrations in tobacco smoke indicates a role for metal i ons in the subsequent toxicity and carcinogenicity of tobacco smoke. T his review summarizes current information pertaining to the role of me tal ions in the toxicity and carcinco-genicity of tobacco smoke, and d escribes the mechanisms that may be involved. Evidence indicates that multiple mechanisms may be involved in the production of reactive oxyg en species involving metal ions in tobacco smoke. Similar mechanisms i nvolving redox cycling with the production of superoxide anion, hydrog en peroxide, and hydroxyl radical appear to be involved for iron, copp er, and chromium. However, some metal ions, such as nickel, lead, cadm ium, mercury, arsenic, and antimony, deplete glutathione and protein-b ound sulfhydryls, thus contributing to an oxidative stress in this man ner. Reactions involved in the production of reactive oxygen species m ay be commonly associated with most membranous fractions of the lungs as mitochondria, microsomes, and peroxisomes. Furthermore, phagocytic cells accumulate in the lungs of smokers, and are another important so urce of reactive oxygen species. These phagocytic cells accumulate met al ions as iron, which catalyzes the formation of reactive oxygen spec ies. Thus, a single metal ion may initiate formation of reactive oxyge n species by more than a single mechanism, and involve more than one o rganelle or cell type. Metal ions can also act as catalysts for the fo rmation of reactive oxygen species and various free radicals by numero us organic, redox cycling constituents such as hydroquinone and catech ol, which are present in tobacco smoke, thus greatly enhancing the pot ential for tissue damaging effects in lungs. Finally, radioactive elem ents such as polonium-210 in tobacco smoke are additional contributing factors to the production of tissue damage. The cumulative and summat ive effects of metal ions are believed to play a significant role in t he toxicity and carcinogenicity of tobacco smoke.