Free-radical chemistry of cigarette smoke and its toxicological implications.

TLDR

Cigarette smoke contains two distinct free‑radical populations—stable tar‑phase radicals and highly reactive gas‑phase radicals—whose effects on lipid peroxidation are complex. The authors propose that the tar‑phase Q/QH₂ polymer and gas‑phase NO/NO₂ radicals act as active redox systems, generating superoxide, hydrogen peroxide, hydroxyl radicals, and oxidizing thiols to disulfides, thereby inactivating alpha‑1‑proteinase inhibitor. These radicals arise from tar‑phase Q/QH₂ polymer reducing oxygen and from steady‑state oxidation of NO to NO₂ that reacts with smoke constituents like isoprene, leading to metastable products implicated in disease processes such as emphysema and cancer. The principal tar‑phase radical was identified as a Q/QH₂ complex, which reacts with DNA in vitro, suggesting potential covalent binding.

Abstract

Cigarette smoke contains two very different populations of free radicals, one in the tar and one in the gas phase. The tar phase contains several relatively stable free radicals; we have identified the principal radical as a quinone/hydroquinone (Q/QH2) complex held in the tarry matrix. We suggest that this Q/QH2 polymer is an active redox system that is capable of reducing molecular oxygen to produce superoxide, eventually leading to hydrogen peroxide and hydroxyl radicals. In addition, we have shown that the principal radical in tar reacts with DNA in vitro, possibly by covalent binding. The gas phase of cigarette smoke contains small oxygen- and carbon-centered radicals that are much more reactive than are the tar-phase radicals. These gas-phase radicals do not arise in the flame, but rather are produced in a steady state by the oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. We suggest that these radicals and the metastable products derived from these radical reactions may be responsible for the inactivation of alpha 1-proteinase inhibitor by fresh smoke. Cigarette smoke oxidizes thiols to disulfides; we suggest the active oxidants are NO and NO2. The effects of smoke on lipid peroxidation are complex, and this is discussed. We also discuss the toxicological implications for the radicals in smoke in terms of a number of radical-mediated disease processes, including emphysema and cancer.