Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles

Our plain-English summary of Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles, by A. Valavanidis, T. Vlachogianni, K. Fiotakis (International Journal of Environmental Research and Public Health, 2009).

The study

• Authors: A. Valavanidis, T. Vlachogianni, K. Fiotakis
• Journal: International Journal of Environmental Research and Public Health
• Published: 2009;6(2):445-62
• Cited by: 383 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS) in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR) and spin-trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O2 (*-)) and hydroxyl (HO(*)) radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT) solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2'-deoxyguanosine (a biomarker for carcinogenesis). Also, we observed synergistic effects in the generation of HO(*), through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc.) and ambient particulate matter (PM), such as PM(10), PM(2.5) and diesel exhaust particles (DEP). The highest synergistic effects was observed with the asbestos fibres (freshly grounded), PM(2.5) and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and "bio-filters" with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase.

In plain English

This was a laboratory chemistry study, not a study of people or animals. The authors used electron paramagnetic resonance (EPR), which detects free radicals, to examine tar and gas-phase smoke from low-, middle- and high-tar cigarettes. The tar held stable radicals, which the authors assigned to a semiquinone system, and lower-tar cigarettes gave smaller signals. Tar dissolved in buffered water produced hydroxyl radicals, and tests with iron-binding chemicals pointed to a role for iron. When freshly ground asbestos fibres (crocidolite and chrysotile) were mixed with tar, their hydroxyl-radical signal was 2.5-3 times higher than without tar. Coal mine dust, talc, urban air particles and diesel exhaust particles also produced more hydroxyl radicals with tar, most for PM2.5 and diesel particles, least for coal dust and talc. Tar alone also formed 8-OHdG, a marker of oxidative DNA damage, from deoxyguanosine, a DNA building block; asbestos plus tar gave the highest value (250 ± 35 µg per 10^6 dG). The authors concluded that cigarette smoke and respirable fibres and dusts act synergistically in producing damaging hydroxyl radicals.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (cell-free, test-tube) chemistry experiments using EPR spectroscopy with spin-trapping and HPLC measurement of 8-OHdG; no human or animal subjects
• Who was studied: No people were studied. Samples were tar and gas-phase smoke from three cigarette types (about 3, 8 and 14 mg tar per cigarette), with five cigarettes smoked per measurement. Comparison particles included PM10 and PM2.5 collected in the center of Athens, Greece, and diesel exhaust particles.
• Exposure: Aqueous cigarette tar mixed in buffer at pH 7.4 with freshly ground asbestos fibres (crocidolite and chrysotile, tested separately) and with coal dust, talc dust, PM10, PM2.5 and diesel exhaust particles
• Main results:
  • Tar from all three cigarette types gave a single broad EPR signal that the authors assigned to a semiquinone radical system. Lower-tar cigarettes gave smaller signals, estimated at about 10^15 spins per gram for low-tar tar and 10^16 to 10^17 spins per gram for high-tar tar.
  • Aqueous tar produced hydroxyl radicals. Adding EDTA increased the signal, and desferrioxamine suppressed it almost completely, which the authors took to suggest a role for iron and other metals.
  • Formation of 8-OHdG from deoxyguanosine, in µg per 10^6 dG (mean ± S.D., n=3): low-tar ACT 120 ± 10, middle-tar 145 ± 12, high-tar 170 ± 20; PM10 plus H2O2 85 ± 4; PM2.5 plus H2O2 100 ± 6; diesel exhaust particles plus H2O2 115 ± 10; freshly ground asbestos fibres (10 mg) plus ACT (50 mg) 250 ± 35. No 8-OHdG results were reported for coal dust or talc.
  • Hydroxyl radical production by mixtures of asbestos fibres and tar was described as doubled, which the authors interpreted as a synergistic effect.
  • In EPR measurements, asbestos fibres showed a signal 2.5-3 times stronger with tar than without it.
  • The other respirable particles also showed a synergistic effect on hydroxyl-radical generation with tar. Among them the effect was highest for PM2.5 and diesel exhaust particles and lowest for coal mine dust and talc.
  • Gas-phase radicals were similar in intensity across all three cigarette types.
• The authors' conclusion: The authors concluded that hydroxyl radicals generated by aqueous cigarette tar can cause oxidative DNA damage, and that cigarette smoke and respirable fibres and dusts act synergistically to increase production of damaging hydroxyl radicals.
• Limitations the authors state:
  • The authors stated that the quantitative comparison of radical concentrations in tar was of limited accuracy.
  • The authors noted that oxidative damage to DNA in the living body is very different from damage to an isolated nucleoside such as deoxyguanosine in solution.

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Carcinogenesis, Synergistic Effect, Carcinogenic, Superoxide, Biomarker, Fenton Reaction.

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